WO2016072496A1 - Alcohol metabolism promoter - Google Patents
Alcohol metabolism promoter Download PDFInfo
- Publication number
- WO2016072496A1 WO2016072496A1 PCT/JP2015/081335 JP2015081335W WO2016072496A1 WO 2016072496 A1 WO2016072496 A1 WO 2016072496A1 JP 2015081335 W JP2015081335 W JP 2015081335W WO 2016072496 A1 WO2016072496 A1 WO 2016072496A1
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- WO
- WIPO (PCT)
- Prior art keywords
- bivalve
- extract
- alcohol metabolism
- hangover
- blood
- Prior art date
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Images
Classifications
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
- A61K35/56—Materials from animals other than mammals
- A61K35/618—Molluscs, e.g. fresh-water molluscs, oysters, clams, squids, octopus, cuttlefish, snails or slugs
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
- A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/715—Polysaccharides, i.e. having more than five saccharide radicals attached to each other by glycosidic linkages; Derivatives thereof, e.g. ethers, esters
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/715—Polysaccharides, i.e. having more than five saccharide radicals attached to each other by glycosidic linkages; Derivatives thereof, e.g. ethers, esters
- A61K31/716—Glucans
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P39/00—General protective or antinoxious agents
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P39/00—General protective or antinoxious agents
- A61P39/02—Antidotes
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- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs
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- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2200/00—Function of food ingredients
- A23V2200/30—Foods, ingredients or supplements having a functional effect on health
- A23V2200/334—Foods, ingredients or supplements having a functional effect on health treating the effects of consuming alcohol, narcotics or other addictive behavior, e.g. treating hangover or reducing blood alcohol levels
Definitions
- the present invention relates to a novel alcohol metabolism promoter.
- Acetaldehyde is an unavoidable product of alcohol metabolism but is highly toxic and forms the cause of unpleasant symptoms such as acute poisoning, gastrointestinal irritations, nausea, headache, hangover, and hangover when alcoholic beverages are consumed excessively. It is generally known to do (Patent Document 1).
- Patent Documents 2 and 3 the development of oral substances for promoting alcohol metabolism and suppressing blood acetaldehyde concentration to a low level has been studied.
- Patent Documents 2 and 3 there is still a need for an oral preparation that can effectively achieve alcohol metabolism promotion or suppression of increase in blood acetaldehyde concentration.
- the inventors of the present invention have recently found that when an extract of a bivalve bivalve containing glycogen is administered to a subject, an increase in the blood concentration of acetaldehyde accompanying alcohol intake can be effectively suppressed.
- the present invention is based on such knowledge.
- an object of the present invention is to provide a novel alcohol metabolism promoter capable of suppressing an increase in the blood concentration of acetaldehyde.
- an alcohol metabolism promoter containing glycogen (2) The alcohol metabolism promoter according to (1), wherein the glycogen is derived from an extract of a bivalve bivalve. (3) The alcohol metabolism promoter according to (1) or (2), wherein the bivalve is an Icelandic guy. (4) An alcohol metabolism promoter containing an extract of a bivalve bivalve. (5) The alcohol metabolism promoter according to (4), wherein the bivalve is an Icelandic guy. (6) The alcohol metabolism promoter according to any one of (1) to (5), which is in the form of a single oral intake unit.
- (11) The method according to (9) or (10), which is a method for preventing hangover or hangover.
- an increase in the blood concentration of acetaldehyde in a subject who has taken alcohol can be effectively suppressed.
- the agent of the present invention is acute poisoning when excessively drinking alcoholic beverages, gastrointestinal irritations, nausea, vomiting, headache, head sensation, body irritation, sleepiness, myalgia, diarrhea, dizziness, feeling of body movement, sickness Or it is advantageous in preventing unpleasant symptoms such as a hangover.
- Alcohol metabolism promoter of the present invention is characterized by containing an extract of a bivalve bivalve. It is a surprising fact that the extract of the bivalve bivalve has a remarkable effect of suppressing the rise in blood acetaldehyde concentration.
- kind of veneroida bivalve is not particularly limited as long as it does not interfere with the effects of the present invention, Kagogai, giant clams, Wadachizarugai, Sudarenaminoko, Ijin'noyumegai, circle Ominaeshi, phantom clams, Konohazakura, Gould's Razor Shell, Namigai and Iceland Guy (Arctica islandica) Etc., but Icelandic guy is preferable.
- An Icelandic guy is a bivalve, usually 3-5 inches in size, also known as the Ocean (Quahog) Clam, and can be collected from 120 to 200 feet deep on the east coast of the United States. Are known.
- the extract of the bivalve bivalve of the present invention may be produced from a natural product or a commercially available product.
- Examples of commercially available products include Sea Watch International Ltd., USA. SW Ocean Clam Juice (CODE 0431) and ESF Ocean Clam Juice (CODE 04ES) manufactured in Japan.
- the extract of the present invention is not particularly limited as long as the effects of the present invention are not hindered, but is preferably an extract of an aqueous medium (such as ethanol, water, or a mixture thereof) of Marsdalena bivalve, more preferably water extraction. It is a thing.
- an aqueous medium such as ethanol, water, or a mixture thereof
- the extract of the present invention is not particularly limited as long as it does not interfere with the effects of the present invention.
- moisture, protein, lipid, ash (mineral: sodium, etc.), carbohydrate (glucose, mucopolysaccharide, glycogen, nucleic acid (DNA) , RNA, etc.).
- the content of each of these components is not particularly limited.
- moisture is 0 to 10% by mass
- protein is 0 to 30% by mass
- lipid is 0 to 5% by mass
- ash is 0 to 5% by mass
- carbohydrates are 50 to 90%. It may be mass%.
- Such a content can be determined by the drying and measurement method described in Example 1.
- the extract of the present invention preferably contains glycogen.
- the content of glycogen is not particularly limited as long as the effect of the present invention is not hindered. For example, it may be 80% by mass or more, and preferably 50 to 90% by mass.
- the molecular weight of the glycogen of the present invention is not particularly limited as long as the effect of the present invention is not hindered, but is preferably 10,000 or more, more preferably 100,000 or more.
- the molecular weight of the shellfish extract of the present invention is not particularly limited as long as the effects of the present invention are not hindered, but is preferably 10,000 or more, more preferably 100,000 or more. Any of the molecular weight glycogen or shellfish extract can be fractionated and concentrated according to the ultrafiltration treatment described in Example 1.
- the method for producing the extract of the present invention is not particularly limited as long as the effects of the present invention are not hindered.
- an extract of an aqueous medium of a bivalve bivalve may be used as it is, and a bivalve bivalve is compressed and pulverized as desired. After boiled or boiled, the extract produced when the edible part is separated from the body may be collected, concentrated, and extracted with an aqueous medium.
- purification treatment, concentration treatment, sterilization treatment and the like using a known method may be performed as desired.
- Examples of the purification treatment include proteolytic enzyme treatment, lipolytic enzyme treatment, filtration treatment, activated carbon treatment, dialysis treatment (electrodialysis, etc.), and centrifugation treatment.
- Examples of the concentration treatment include ultrafiltration treatment and freeze-drying treatment.
- purification process is preferable when decomposing
- Each of the above treatments may be performed at any stage of the method for producing the extract as long as the effects of the present invention are not hindered.
- the extract of the present invention may be in any form of solid, powder, granule, liquid or slurry.
- the extract of the present invention when prepared in a powder form or a solid form, it can be solidified or powdered by, for example, a freeze drying method or a spray drying method.
- the extract of the present invention may be used as it is as a dosage form for promoting alcohol metabolism, suppressing an increase in blood acetaldehyde concentration, or preventing hangover or hangover.
- Excipients, binders, preservatives, stabilizers It may be mixed with pharmacologically or orally acceptable components such as perfumes and liquid media to form a dosage form.
- the dosage form of the present invention is not particularly limited, and examples thereof include tablets, granules, capsules, and drinks.
- the agent of the present invention is preferably composed of a single oral intake unit form so as to be an effective amount for suppressing an increase in blood acetaldehyde concentration.
- the unit in the agent of the present invention may contain 4 mg or more, and more preferably 8 mg or more of glycogen in terms of dry mass as a single oral intake.
- the agent of the present invention contains glycogen in an amount of 80% by mass or more, the agent of the present invention is usually taken by an adult for 5 to 5000 mg per day, preferably 10 to 2000 mg once or continuously. It is preferable.
- the agent of the present invention is preferably provided in a form packaged in a single oral intake unit.
- unit packaging forms per oral intake include forms that define a certain amount in packs, containers, etc., and on their surfaces, component display of oral intake and alcohol metabolism promotion, Use indications such as suppression of increase in blood acetaldehyde concentration or prevention of hangover or hangover may be attached.
- Suitable examples of such unit package forms include supplements, pharmaceutical preparations and the like.
- the agent of the present invention it is possible to effectively suppress an increase in blood acetaldehyde concentration in a subject who has ingested alcohol, and to effectively promote alcohol metabolism and prevent hangover or hangover. Therefore, according to one aspect of the present invention, there is provided the use of an extract of glycogen or a bivalve bivalve in the manufacture of an alcohol metabolism promoter. According to another aspect, there is provided use of an extract of glycogen or a bivalve bivalve in the manufacture of an agent for suppressing an increase in blood acetaldehyde concentration. Furthermore, according to another aspect, there is provided the use of an extract of glycogen or a bivalve bivalve in the manufacture of an agent for the prevention of hangover or hangover.
- the administration schedule of the agent of the present invention can be appropriately set by those skilled in the art depending on the age, sex and symptoms of the subject as long as the effects of the present invention are not hindered.
- the agent of the present invention may be administered to a subject continuously or in a single dose. According to a preferred embodiment, it is preferable to administer a single oral intake unit amount of the agent of the present invention to the subject at least once before, during or after the intake of alcohol.
- a sickness or hangover comprising ingesting an effective amount of the agent of the present invention for suppressing an increase in blood acetaldehyde concentration to a subject in need thereof.
- a prevention method is provided.
- the method for preventing hangover or hangover excludes medical practice for humans.
- the method for preventing hangover or hangover of the present invention is preferably a method for promoting alcohol metabolism, and more preferably a method for suppressing an increase in blood acetaldehyde concentration.
- the “effective amount for suppressing an increase in the blood acetaldehyde concentration” can be composed of the above-mentioned single oral intake unit.
- prevention includes not only treating an established disease state / symptom, but also preventing a disease state / symptom that may be established in the future.
- the subject is a mammal, for example, a rodent, a dog, a cat, a cow, a primate, and the like, preferably a human, more preferably a human before, during or after alcohol intake.
- the subject may be a healthy person or a sick person, but is preferably a healthy person before, during or after taking alcohol.
- the liver function item result of blood test is “A” or “B” (“no abnormality” or “mild abnormality” based on the Judgment Category (revised April 1, 2014) )).
- the blood liver function parameters of such healthy persons have an AST (GOT) value of 35 U / L or less, an ALT (GPT) of 40 U / L or less, and ⁇ -GTP.
- the value satisfies the range of 80 U / L or less.
- JIS standards Japanese Industrial Standards
- Example 1 Manufacture of Marsdalegai bivalve extract (Ocean Clam Concentrate / Sea Watch International, Ltd., source of Marsdalegai bivalve; 3 to 200 miles off the coast of Virginia from Massachusetts, USA Sea area) 8200 g of 4 times amount of purified water was added to 2200 g to obtain a diluted solution. Next, 0.08% of protease (Amanoenzyme Protease P “Amano” 3SD 1.76g) and peptidase (Amanoenzyme Peptidase R 1.76g) equivalent to the concentrate of the bivalve bivalve are added, and at 35 ° C. for 5 hours. The mixture was stirred and subjected to enzymatic decomposition.
- protease Amanoenzyme Protease P “Amano” 3SD 1.76g
- peptidase Amanoenzyme Peptidase R 1.76g
- the obtained enzyme treatment solution was heated at 75 ° C. for 2 hours for enzyme deactivation and sterilization treatment, and then allowed to cool. 10925 g of the resulting solution was centrifuged (4200 rpm / 10 min; HimacCR7 manufactured by Hitachi Koki Co., Ltd.), and 10666 g of the separated supernatant was filtered (POLYSEP II 10 ′′, 1.2 ⁇ m manufactured by Merck) to obtain 10344 g of filtrate. Further, the obtained filtrate was subjected to an ultrafiltration treatment (SARTOCON Slice Cassette Hydrosart 100K, manufactured by Sartorius Stedim Japan) and concentrated to 1794 g, which was added to the filtrate for desalting and purification.
- SARTOCON Slice Cassette Hydrosart 100K manufactured by Sartorius Stedim Japan
- the concentrated solution was spray-dried using a spray dryer (L-8i type / Atomizer 25000 rpm 170 ° C.-85 ° C., manufactured by Okawara Chemical Industries Co., Ltd.), and 193 g of extract powder of the bivalve bivalve shellfish.
- a spray dryer Li-8i type / Atomizer 25000 rpm 170 ° C.-85 ° C., manufactured by Okawara Chemical Industries Co., Ltd.
- a solution prepared by dissolving the extract powder at a concentration of 50 mg / mL in water for injection (Fuso Pharmaceutical Co., Ltd.) was orally administered once a day in an amount of 10 mL / kg (administration). Amount 500 mg / kg).
- the obtained blood was mixed with an equal amount of ice-cold 1 mol / L perchloric acid, centrifuged at 4 ° C., 12,000 g ⁇ 3 minutes, and the supernatant was collected.
- the obtained supernatant was aliquoted into a blood ethanol concentration measurement sample and a blood acetaldehyde concentration measurement sample, and stored at ⁇ 80 ° C. until measurement.
- Blood ethanol concentration was measured using F kit ethanol (JK International Co., Ltd.), and blood acetaldehyde concentration was measured using F kit acetaldehyde (JK International Co., Ltd.).
- the statistical test of the measurement results is performed by F test for equal variance of each group, comparison between groups in case of equal variance is performed by Student-t test, and comparison between groups in case of unequal variance is Aspin- Welch's approximate test was performed.
- a solution prepared by dissolving the extract powder at a concentration of 50 mg / mL in water for injection (Fuso Pharmaceutical Co., Ltd.) was orally administered once a day in an amount of 10 mL / kg (administration). Amount 500 mg / kg).
- water for injection was administered once a day in an amount of 10 mL / kg.
- a 25% ethanol / physiological saline solution was administered into the tail vein so that the ethanol dosage was 1 g / kg.
- a disposable syringe and needle in which heparin sodium (Novo-Heparin injection 10,000 units, Mochida Pharmaceutical Co., Ltd.) was placed in advance Used, approximately 0.5 mL of blood at each time point was collected from the jugular vein without anesthesia.
- the obtained blood was mixed with an equal amount of ice-cold 1 mol / L perchloric acid, centrifuged at 4 ° C., 12,000 g ⁇ 3 minutes, and the supernatant was collected.
- the obtained supernatant was aliquoted into a blood ethanol concentration measurement sample and a blood acetaldehyde concentration measurement sample, and stored at ⁇ 80 ° C. until measurement.
- Blood ethanol concentration was measured using F kit ethanol (JK International Co., Ltd.), and blood acetaldehyde concentration was measured using F kit acetaldehyde (JK International Co., Ltd.).
- the statistical test of the measurement results is performed by F test for equal variance of each group, comparison between groups in case of equal variance is performed by Student-t test, and comparison between groups in case of unequal variance is Aspin- Welch's approximate test was performed.
- a solution of the extract powder dissolved in water for injection (Fuso Pharmaceutical Co., Ltd.) at a concentration of 50 mg / mL is orally administered once a day in an amount of 10 mL / kg. Administration (dose 500 mg / kg).
- an aqueous glucose solution Japanese Pharmacopoeia glucose injection solution, glucose concentration 5%, manufactured by Otsuka Pharmaceutical Co., Ltd.
- a 25% ethanol / physiological saline solution was administered into the tail vein so that the ethanol dosage was 1 g / kg.
- a disposable syringe and needle containing heparin sodium (Novo-Heparin injection 10,000 units, Mochida Pharmaceutical Co., Ltd.) and a needle were used under anesthesia without anesthesia.
- the obtained blood was centrifuged (1800 g, 4 ° C., 15 minutes), and plasma was separated and stored frozen at ⁇ 80 ° C.
- An equal amount of 1 mol / L perchloric acid was added to and mixed with freeze-thawed plasma, centrifuged, and the supernatant was collected and neutralized with half of 0.7 mol / L trisodium phosphate.
- the sample was used as a sample for measuring plasma acetaldehyde concentration.
- the plasma acetaldehyde concentration was measured using F kit acetaldehyde (JK International Co., Ltd.).
- the statistical test of the measurement results is performed by F test for equal variance of each group, the comparison between groups in the case of equal variance is performed by Student-t test, and the comparison between groups in the case of unequal variance is Aspin- Welch's approximate test was performed.
- Example 5 Examination of the action to prevent hangover and hangover by using extract powder of Bivalvia bivalve 11 healthy subjects (9 men, 2 women, age 23-55) were selected. According to the Judgment Category (revised on April 1, 2014) of the Japan Ningen Dock Society, all subjects were those whose liver function items in blood tests were classified as “A” or “B”.
- one of the sachets contained in the aluminum bag shall contain the test date of the first period and the other shall contain the test day of the second period. Oita. This is to adjust the subject to take the test sample on one of the two phases and the placebo sample on the other.
- the number of people in each group in each period was 5 or 6, respectively, and the number of people in each group in both periods was adjusted in advance to be the same number.
- the subject selected a sample from an aluminum bag according to the test date described in the sachet, and ingested the sample together with 100 mL of drinking water. Immediately after taking the sample, all subjects took the same meal and took a slightly higher amount of alcohol (28 to 143 g, average 94 g) over the course of 2 to 3 hours.
- the second test was conducted. Specifically, the subject ingested the sample in the other sachet remaining in the same aluminum bag as in the first period with 100 mL of drinking water. Here, the subject was instructed in advance to take the same content and amount of meal and alcohol as in the first period immediately after taking the sample. About 10 hours after the end of alcohol consumption, each subject evaluated subjective symptoms as in the first period.
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Abstract
The present invention relates to an agent for effectively suppressing an increase in blood-acetaldehyde concentration. More specifically, the present invention relates to an alcohol metabolism promoter containing glycogen obtained from a Veneroida bivalve.
Description
本特許出願は、２０１４年１１月７日に出願された日本国特許出願２０１４－２２７３８７号に基づく優先権の主張を伴うものであり、かかる先の特許出願における全開示内容は、引用することにより本明細書の一部とされる。
This patent application is accompanied by a claim of priority based on Japanese Patent Application No. 2014-227387 filed on November 7, 2014, and the entire disclosure in such earlier patent application is incorporated by reference. It is made a part of this specification.
本発明は、新規なアルコール代謝促進剤に関する。
The present invention relates to a novel alcohol metabolism promoter.
アセトアルデヒドは、アルコール代謝上不可避的な生成物であるが強い毒性があり、アルコール飲料を過度に摂取したときの急性中毒、胃腸のムカツキ、吐き気、頭痛、悪酔い、二日酔い等の不快症状の原因を形成することが一般的に知られている（特許文献１）。
Acetaldehyde is an unavoidable product of alcohol metabolism but is highly toxic and forms the cause of unpleasant symptoms such as acute poisoning, gastrointestinal irritations, nausea, headache, hangover, and hangover when alcoholic beverages are consumed excessively. It is generally known to do (Patent Document 1).
アルコールを過剰に摂取すると、肝臓でのアルコール代謝は選択的に亢進し、その結果として肝臓内の代謝系に大きな変動が生じうる。摂取したアルコールの大部分は、肝細胞のサイトゾールに存在するアルコール脱水素酵素系を介してアセトアルデヒドとなり、アセトアルデヒドはさらにアルデヒド脱水素酵素による脱水素反応を受けて通常であれば酢酸に変換される。しかしながら、アルコール摂取量が多すぎたり、体調が悪くアルコールの代謝が遅れたりすると、アセトアルデヒドが処理しきれなくなり、血中のアセトアルデヒド濃度が高くなり、アセトアルデヒドの毒性に起因した悪酔い、二日酔い等の不快症状が生じうる。よって、アルコール代謝を促進して、アセトアルデヒドの血中濃度の上昇をいかに抑制するかが悪酔いや二日酔い等の不快症状の予防に重要である。
If excessive alcohol is consumed, alcohol metabolism in the liver is selectively increased, and as a result, a large fluctuation may occur in the metabolic system in the liver. Most of the ingested alcohol is converted to acetaldehyde through the alcohol dehydrogenase system present in cytosol of hepatocytes, and acetaldehyde is further converted to acetic acid by dehydrogenation reaction by aldehyde dehydrogenase. . However, if the alcohol intake is too high or the physical condition is poor and the metabolism of alcohol is delayed, acetaldehyde cannot be processed completely, the blood acetaldehyde concentration becomes high, and unpleasant symptoms such as hangover and hangover due to acetaldehyde toxicity Can occur. Therefore, it is important to prevent unpleasant symptoms such as hangovers and hangovers by promoting alcohol metabolism and suppressing the increase in the blood concentration of acetaldehyde.
近年、アルコール代謝を促進、血中アセトアルデヒド濃度を低レベルに抑制するための経口物質の開発が検討されている（特許文献２、特許文献３）。しかしながら、依然として、アルコール代謝促進または血中アセトアルデヒド濃度の上昇抑制を効果的に達成しうる経口剤が必要とされている。
In recent years, the development of oral substances for promoting alcohol metabolism and suppressing blood acetaldehyde concentration to a low level has been studied (Patent Documents 2 and 3). However, there is still a need for an oral preparation that can effectively achieve alcohol metabolism promotion or suppression of increase in blood acetaldehyde concentration.
一方、貝類の加工品について、健康増進機能を有する機能性食品として利用することが報告されている。例えば、ムラサキイガイ軟体部およびムラサキイガイエキスのいずれかを用い、ＡＳＴおよびＡＬＴ値の増加を抑制して肝障害を抑制することが知られている（特許文献４）。
On the other hand, it is reported that processed products of shellfish are used as functional foods having a health promotion function. For example, it is known to use either a mussel soft body part or a mussel extract and suppress an increase in AST and ALT values to suppress liver damage (Patent Document 4).
しかしながら、マルスダレガイ目二枚貝と、血中アセトアルデヒド濃度の上昇抑制作用との関係については何ら報告されていない。
However, there is no report on the relationship between the bivalve bivalve and the effect of suppressing the increase in blood acetaldehyde concentration.
本発明者らは、今般、グリコーゲンを含有するマルスダレガイ目二枚貝の抽出物を対象に投与したところ、アルコール摂取に伴うアセトアルデヒドの血中濃度の上昇を効果的に抑制しうることを見出した。本発明は、かかる知見に基づくものである。
The inventors of the present invention have recently found that when an extract of a bivalve bivalve containing glycogen is administered to a subject, an increase in the blood concentration of acetaldehyde accompanying alcohol intake can be effectively suppressed. The present invention is based on such knowledge.
したがって、本発明は、アセトアルデヒドの血中濃度の上昇を抑制しうる新規なアルコール代謝促進剤の提供をその目的としている。
Therefore, an object of the present invention is to provide a novel alcohol metabolism promoter capable of suppressing an increase in the blood concentration of acetaldehyde.
本発明によれば、以下の発明が提供される。
（１）グリコーゲンを含有する、アルコール代謝促進剤。
（２）上記グリコーゲンがマルスダレガイ目二枚貝の抽出物に由来する、（１）に記載のアルコール代謝促進剤。
（３）上記二枚貝がアイスランドガイである、（１）または（２）に記載のアルコール代謝促進剤。
（４）マルスダレガイ目二枚貝の抽出物を含有する、アルコール代謝促進剤。
（５）上記二枚貝がアイスランドガイである、（４）に記載のアルコール代謝促進剤。
（６）一回の経口摂取量単位の形態である、（１）～（５）のいずれかに記載のアルコール代謝促進剤。
（７）血中アセトアルデヒド濃度の上昇抑制剤である、（１）～（６）のいずれかに記載のアルコール代謝促進剤。
（８）悪酔いまたは二日酔いの防止剤である、（１）～（７）のいずれかに記載のアルコール代謝促進剤。
（９）血中アセトアルデヒド濃度の上昇抑制方法であって、それを必要とする対象にグリコーゲンまたはマルスダレガイ目二枚貝の抽出物の有効量を摂取させることを含んでなる、方法。
（１０）アルコール代謝促進方法である、（９）に記載の方法。
（１１）悪酔いまたは二日酔いの防止方法である、（９）または（１０）に記載の方法。
（１２）血中アセトアルデヒド濃度の上昇抑制剤の製造における、グリコーゲンまたはマルスダレガイ目二枚貝の抽出物の使用。
（１３）上記剤がアルコール代謝促進剤である、（１２）に記載の使用。
（１４）上記剤が悪酔いまたは二日酔いの防止剤である、（１２）または（１３）に記載の使用。
（１５）血中アセトアルデヒド濃度の上昇抑制剤としての、グリコーゲンまたはマルスダレガイ目二枚貝の抽出物の使用。 According to the present invention, the following inventions are provided.
(1) An alcohol metabolism promoter containing glycogen.
(2) The alcohol metabolism promoter according to (1), wherein the glycogen is derived from an extract of a bivalve bivalve.
(3) The alcohol metabolism promoter according to (1) or (2), wherein the bivalve is an Icelandic guy.
(4) An alcohol metabolism promoter containing an extract of a bivalve bivalve.
(5) The alcohol metabolism promoter according to (4), wherein the bivalve is an Icelandic guy.
(6) The alcohol metabolism promoter according to any one of (1) to (5), which is in the form of a single oral intake unit.
(7) The alcohol metabolism promoter according to any one of (1) to (6), wherein the alcohol metabolism promoter is an inhibitor for increasing the blood acetaldehyde concentration.
(8) The alcohol metabolism promoter according to any one of (1) to (7), which is an agent for preventing hangover or hangover.
(9) A method for suppressing an increase in blood acetaldehyde concentration, which comprises allowing a subject in need thereof to take an effective amount of an extract of glycogen or a bivalve bivalve.
(10) The method according to (9), which is a method for promoting alcohol metabolism.
(11) The method according to (9) or (10), which is a method for preventing hangover or hangover.
(12) Use of an extract of glycogen or a bivalve bivalve in the production of an inhibitor for increasing the blood acetaldehyde concentration.
(13) The use according to (12), wherein the agent is an alcohol metabolism promoter.
(14) The use according to (12) or (13), wherein the agent is an agent for preventing hangover or hangover.
(15) Use of an extract of glycogen or a bivalve bivalve as an inhibitor of an increase in blood acetaldehyde concentration.
（１）グリコーゲンを含有する、アルコール代謝促進剤。
（２）上記グリコーゲンがマルスダレガイ目二枚貝の抽出物に由来する、（１）に記載のアルコール代謝促進剤。
（３）上記二枚貝がアイスランドガイである、（１）または（２）に記載のアルコール代謝促進剤。
（４）マルスダレガイ目二枚貝の抽出物を含有する、アルコール代謝促進剤。
（５）上記二枚貝がアイスランドガイである、（４）に記載のアルコール代謝促進剤。
（６）一回の経口摂取量単位の形態である、（１）～（５）のいずれかに記載のアルコール代謝促進剤。
（７）血中アセトアルデヒド濃度の上昇抑制剤である、（１）～（６）のいずれかに記載のアルコール代謝促進剤。
（８）悪酔いまたは二日酔いの防止剤である、（１）～（７）のいずれかに記載のアルコール代謝促進剤。
（９）血中アセトアルデヒド濃度の上昇抑制方法であって、それを必要とする対象にグリコーゲンまたはマルスダレガイ目二枚貝の抽出物の有効量を摂取させることを含んでなる、方法。
（１０）アルコール代謝促進方法である、（９）に記載の方法。
（１１）悪酔いまたは二日酔いの防止方法である、（９）または（１０）に記載の方法。
（１２）血中アセトアルデヒド濃度の上昇抑制剤の製造における、グリコーゲンまたはマルスダレガイ目二枚貝の抽出物の使用。
（１３）上記剤がアルコール代謝促進剤である、（１２）に記載の使用。
（１４）上記剤が悪酔いまたは二日酔いの防止剤である、（１２）または（１３）に記載の使用。
（１５）血中アセトアルデヒド濃度の上昇抑制剤としての、グリコーゲンまたはマルスダレガイ目二枚貝の抽出物の使用。 According to the present invention, the following inventions are provided.
(1) An alcohol metabolism promoter containing glycogen.
(2) The alcohol metabolism promoter according to (1), wherein the glycogen is derived from an extract of a bivalve bivalve.
(3) The alcohol metabolism promoter according to (1) or (2), wherein the bivalve is an Icelandic guy.
(4) An alcohol metabolism promoter containing an extract of a bivalve bivalve.
(5) The alcohol metabolism promoter according to (4), wherein the bivalve is an Icelandic guy.
(6) The alcohol metabolism promoter according to any one of (1) to (5), which is in the form of a single oral intake unit.
(7) The alcohol metabolism promoter according to any one of (1) to (6), wherein the alcohol metabolism promoter is an inhibitor for increasing the blood acetaldehyde concentration.
(8) The alcohol metabolism promoter according to any one of (1) to (7), which is an agent for preventing hangover or hangover.
(9) A method for suppressing an increase in blood acetaldehyde concentration, which comprises allowing a subject in need thereof to take an effective amount of an extract of glycogen or a bivalve bivalve.
(10) The method according to (9), which is a method for promoting alcohol metabolism.
(11) The method according to (9) or (10), which is a method for preventing hangover or hangover.
(12) Use of an extract of glycogen or a bivalve bivalve in the production of an inhibitor for increasing the blood acetaldehyde concentration.
(13) The use according to (12), wherein the agent is an alcohol metabolism promoter.
(14) The use according to (12) or (13), wherein the agent is an agent for preventing hangover or hangover.
(15) Use of an extract of glycogen or a bivalve bivalve as an inhibitor of an increase in blood acetaldehyde concentration.
本発明によれば、アルコール摂取した対象におけるアセトアルデヒドの血中濃度の上昇を効果的に抑制することができる。本発明の剤は、アルコール飲料を過度に摂取したときの急性中毒、胃腸のムカツキ、吐き気、嘔吐、頭痛、頭重感、からだのだるさ、眠気、筋肉痛、下痢、めまい、体の動揺感、悪酔いまたは二日酔い等の不快症状を防止する上で有利である。
According to the present invention, an increase in the blood concentration of acetaldehyde in a subject who has taken alcohol can be effectively suppressed. The agent of the present invention is acute poisoning when excessively drinking alcoholic beverages, gastrointestinal irritations, nausea, vomiting, headache, head sensation, body irritation, sleepiness, myalgia, diarrhea, dizziness, feeling of body movement, sickness Or it is advantageous in preventing unpleasant symptoms such as a hangover.
アルコール代謝促進剤
本発明のアルコール代謝促進剤は、マルスダレガイ目二枚貝の抽出物を含有することを一つの特徴としている。マルスダレガイ目二枚貝の抽出物が顕著な血中アセトアルデヒド濃度の上昇抑制効果を奏することは意外な事実である。 Alcohol metabolism promoter The alcohol metabolism promoter of the present invention is characterized by containing an extract of a bivalve bivalve. It is a surprising fact that the extract of the bivalve bivalve has a remarkable effect of suppressing the rise in blood acetaldehyde concentration.
本発明のアルコール代謝促進剤は、マルスダレガイ目二枚貝の抽出物を含有することを一つの特徴としている。マルスダレガイ目二枚貝の抽出物が顕著な血中アセトアルデヒド濃度の上昇抑制効果を奏することは意外な事実である。 Alcohol metabolism promoter The alcohol metabolism promoter of the present invention is characterized by containing an extract of a bivalve bivalve. It is a surprising fact that the extract of the bivalve bivalve has a remarkable effect of suppressing the rise in blood acetaldehyde concentration.
マルスダレガイ目二枚貝の種類は、本発明の効果を妨げない限り特に限定されず、カゴガイ、オオシャコガイ、ワダチザルガイ、スダレナミノコ、イジンノユメガイ、マルオミナエシ、マボロシハマグリ、コノハザクラ、マテガイ、ナミガイやアイスランドガイ (Arctica islandica) 等が挙げられるが、好ましくはアイスランドガイである。アイスランドガイは、海ホンビノスガイ（Ocean(Quahog) Clam）とも称される通常3～5インチ程度のサイズの二枚貝であり、アメリカ東海岸においては水深120～200フィートの海域で採取することができることが知られている。
Kind of veneroida bivalve is not particularly limited as long as it does not interfere with the effects of the present invention, Kagogai, giant clams, Wadachizarugai, Sudarenaminoko, Ijin'noyumegai, circle Ominaeshi, phantom clams, Konohazakura, Gould's Razor Shell, Namigai and Iceland Guy (Arctica islandica) Etc., but Icelandic guy is preferable. An Icelandic guy is a bivalve, usually 3-5 inches in size, also known as the Ocean (Quahog) Clam, and can be collected from 120 to 200 feet deep on the east coast of the United States. Are known.
本発明のマルスダレガイ目二枚貝の抽出物は、天然物から製造してもよく、市販品を用いてもよい。市販品としては、例えば、アメリカのＳｅａ Ｗａｔｃｈ Ｉｎｔｅｒｎａｔｉｏｎａｌ Ｌｔｄ．で製造されたＳＷ Ｏｃｅａｎ Ｃｌａｍ Ｊｕｉｃｅ（ＣＯＤＥ ０４３１）やＥＳＦ Ｏｃｅａｎ Ｃｌａｍ Ｊｕｉｃｅ（ＣＯＤＥ ０４ＥＳ）等が挙げられる。
The extract of the bivalve bivalve of the present invention may be produced from a natural product or a commercially available product. Examples of commercially available products include Sea Watch International Ltd., USA. SW Ocean Clam Juice (CODE 0431) and ESF Ocean Clam Juice (CODE 04ES) manufactured in Japan.
本発明の抽出物は、本発明の効果を妨げない限り特に限定されないが、好ましくはマルスダレガイ目二枚貝の水性媒体（エタノール、水、またはそれらの混合物等）による抽出物であり、より好ましくは水抽出物である。
The extract of the present invention is not particularly limited as long as the effects of the present invention are not hindered, but is preferably an extract of an aqueous medium (such as ethanol, water, or a mixture thereof) of Marsdalena bivalve, more preferably water extraction. It is a thing.
また、本発明の抽出物は、本発明の効果を妨げない限り特に限定されず、例えば、水分、タンパク質、脂質、灰分（ミネラル：ナトリウム等）、炭水化物（グルコース、ムコ多糖、グリコーゲン、核酸（ＤＮＡ、ＲＮＡ等）等）を含有していてもよい。これら各成分の含有率は特に限定されないが、例えば、乾物換算で、水分０～１０質量％、タンパク質０～３０質量％、脂質０～５質量％、灰分０～５質量％、炭水化物５０～９０質量％であってもよい。かかる含有率は、実施例１に記載の乾燥および測定方法により決定することができる。
The extract of the present invention is not particularly limited as long as it does not interfere with the effects of the present invention. For example, moisture, protein, lipid, ash (mineral: sodium, etc.), carbohydrate (glucose, mucopolysaccharide, glycogen, nucleic acid (DNA) , RNA, etc.). The content of each of these components is not particularly limited. For example, in terms of dry matter, moisture is 0 to 10% by mass, protein is 0 to 30% by mass, lipid is 0 to 5% by mass, ash is 0 to 5% by mass, and carbohydrates are 50 to 90%. It may be mass%. Such a content can be determined by the drying and measurement method described in Example 1.
また、本発明の抽出物は、グリコーゲンを含有していることが好ましい。グリコーゲンの含量は、本発明の効果を妨げない限り特に限定されないが、例えば、８０質量％以上であってもよく、好ましくは５０～９０質量％である。
In addition, the extract of the present invention preferably contains glycogen. The content of glycogen is not particularly limited as long as the effect of the present invention is not hindered. For example, it may be 80% by mass or more, and preferably 50 to 90% by mass.
また、本発明のグリコーゲンの分子量は、本発明の効果を妨げない限り特に限定されないが、好ましくは1万以上であり、より好ましくは１０万以上である。また、本発明の貝抽出物の分子量は、本発明の効果を妨げない限り特に限定されないが、好ましくは1万以上であり、より好ましくは１０万以上である。上記分子量のグリコーゲンまたは貝抽出物はいずれも、実施例１記載の限外濾過処理に準じて分画し、濃縮することができる。
Further, the molecular weight of the glycogen of the present invention is not particularly limited as long as the effect of the present invention is not hindered, but is preferably 10,000 or more, more preferably 100,000 or more. Further, the molecular weight of the shellfish extract of the present invention is not particularly limited as long as the effects of the present invention are not hindered, but is preferably 10,000 or more, more preferably 100,000 or more. Any of the molecular weight glycogen or shellfish extract can be fractionated and concentrated according to the ultrafiltration treatment described in Example 1.
本発明の抽出物の製造方法は、本発明の効果を妨げない限り特に限定されず、例えば、マルスダレガイ目二枚貝の水性媒体による抽出物をそのまま用いてもよく、マルスダレガイ目二枚貝を所望により圧縮、粉砕しまたはボイル後、可食部を身から分離する際に生じるエキスを回収、濃縮し、水性媒体で抽出することにより取得してもよい。さらに、本発明の抽出物の製造方法においては、公知手法を用いた精製処理、濃縮処理、滅菌処理等を所望により実施してもよい。上記精製処理の例としては、タンパク質分解酵素処理、脂質分解酵素処理、ろ過処理、活性炭処理、透析処理（電気透析等）、遠心分離処理等が挙げられる。また、濃縮処理の例としては、限外濾過処理、凍結乾燥処理等が挙げられる。上記精製処理は、二枚貝中のグリコーゲン以外の成分を分解除去し、抽出物を濃縮してグリコーゲン含有濃度を上昇させる上で好ましい。かかる上記各処理は、本発明の効果を妨げない限り、抽出物の製造方法のいずれの段階で行ってもよい。
The method for producing the extract of the present invention is not particularly limited as long as the effects of the present invention are not hindered.For example, an extract of an aqueous medium of a bivalve bivalve may be used as it is, and a bivalve bivalve is compressed and pulverized as desired. After boiled or boiled, the extract produced when the edible part is separated from the body may be collected, concentrated, and extracted with an aqueous medium. Furthermore, in the method for producing the extract of the present invention, purification treatment, concentration treatment, sterilization treatment and the like using a known method may be performed as desired. Examples of the purification treatment include proteolytic enzyme treatment, lipolytic enzyme treatment, filtration treatment, activated carbon treatment, dialysis treatment (electrodialysis, etc.), and centrifugation treatment. Examples of the concentration treatment include ultrafiltration treatment and freeze-drying treatment. The said refinement | purification process is preferable when decomposing | disassembling and removing components other than glycogen in a bivalve, concentrating an extract, and raising a glycogen containing density | concentration. Each of the above treatments may be performed at any stage of the method for producing the extract as long as the effects of the present invention are not hindered.
また、本発明の抽出物は、固形状、粉末状、顆粒状、液状またはスラリー状のいずれの形態であってもよい。
Further, the extract of the present invention may be in any form of solid, powder, granule, liquid or slurry.
また、本発明の抽出物を粉末状または固形状に調製する場合、例えば、凍結乾燥法またはスプレードライ法によって固形化または粉末化することができる。
Further, when the extract of the present invention is prepared in a powder form or a solid form, it can be solidified or powdered by, for example, a freeze drying method or a spray drying method.
また、本発明の抽出物はそのまま、アルコール代謝促進、血中アセトアルデヒド濃度の上昇抑制、あるいは悪酔いまたは二日酔いの防止のための剤型としてもよく、賦形剤、結合剤、防腐剤、安定化剤、香料、液媒体等の薬理学上または経口摂取上許容可能な成分とともに混合して剤型としてもよい。
In addition, the extract of the present invention may be used as it is as a dosage form for promoting alcohol metabolism, suppressing an increase in blood acetaldehyde concentration, or preventing hangover or hangover. Excipients, binders, preservatives, stabilizers It may be mixed with pharmacologically or orally acceptable components such as perfumes and liquid media to form a dosage form.
本発明の剤型は、特に制限されないが、例えば、錠剤、顆粒剤、カプセル剤、ドリンク剤等が挙げられる。
The dosage form of the present invention is not particularly limited, and examples thereof include tablets, granules, capsules, and drinks.
また、本発明の剤は、血中アセトアルデヒド濃度の上昇抑制のための有効量となるように、一回の経口摂取量単位の形態から構成されることが好ましい。本発明の剤における該単位は、一回の経口摂取量として、乾燥質量換算で、好ましくは４ｍｇ以上、より好ましくは８ｍｇ以上のグリコーゲンを含有していてもよい。また、本発明の剤がグリコーゲンを８０質量％以上含有する場合、本発明の剤は通常、成人１人、１日当たり、５～５０００ｍｇ、好ましくは、１０～２０００ｍｇ一回若しくは継続的に摂取されることが好ましい。
In addition, the agent of the present invention is preferably composed of a single oral intake unit form so as to be an effective amount for suppressing an increase in blood acetaldehyde concentration. The unit in the agent of the present invention may contain 4 mg or more, and more preferably 8 mg or more of glycogen in terms of dry mass as a single oral intake. When the agent of the present invention contains glycogen in an amount of 80% by mass or more, the agent of the present invention is usually taken by an adult for 5 to 5000 mg per day, preferably 10 to 2000 mg once or continuously. It is preferable.
さらに、本発明の剤は、一回の経口摂取量単位で包装された形態で提供することが好ましい。一回の経口摂取量当たりの単位包装形態としては、パック、容器等で一定量を規定する形態が挙げられ、それらの表面には一回の経口摂取量の成分表示、および、アルコール代謝促進、血中アセトアルデヒド濃度の上昇抑制、あるいは悪酔いまたは二日酔いの防止等の用途表示を付していてもよい。かかる単位包装形態の好適な例としては、サプリメント、医薬製剤等が挙げられる。
Furthermore, the agent of the present invention is preferably provided in a form packaged in a single oral intake unit. Examples of unit packaging forms per oral intake include forms that define a certain amount in packs, containers, etc., and on their surfaces, component display of oral intake and alcohol metabolism promotion, Use indications such as suppression of increase in blood acetaldehyde concentration or prevention of hangover or hangover may be attached. Suitable examples of such unit package forms include supplements, pharmaceutical preparations and the like.
本発明の剤によれば、アルコールを摂取した対象における血中アセトアルデヒド濃度の上昇を効果的に抑制することができ、アルコール代謝促進、悪酔いまたは二日酔いの防止を効果的に実施することができる。したがって、本発明の一つの態様によれば、アルコール代謝促進剤の製造における、グリコーゲンまたはマルスダレガイ目二枚貝の抽出物の使用が提供される。また、別の態様によれば、血中アセトアルデヒド濃度の上昇抑制剤の製造における、グリコーゲンまたはマルスダレガイ目二枚貝の抽出物の使用が提供される。さらに、別の態様によれば、悪酔いまたは二日酔いの防止剤の製造における、グリコーゲンまたはマルスダレガイ目二枚貝の抽出物の使用が提供される。
According to the agent of the present invention, it is possible to effectively suppress an increase in blood acetaldehyde concentration in a subject who has ingested alcohol, and to effectively promote alcohol metabolism and prevent hangover or hangover. Therefore, according to one aspect of the present invention, there is provided the use of an extract of glycogen or a bivalve bivalve in the manufacture of an alcohol metabolism promoter. According to another aspect, there is provided use of an extract of glycogen or a bivalve bivalve in the manufacture of an agent for suppressing an increase in blood acetaldehyde concentration. Furthermore, according to another aspect, there is provided the use of an extract of glycogen or a bivalve bivalve in the manufacture of an agent for the prevention of hangover or hangover.
本発明の剤の投与計画は、本発明の効果を妨げない限り、対象の年齢、性別、症状に応じて当業者が適宜設定することができる。本発明の剤は、連続的に対象に投与してもよく、単回で投与してもよい。好ましい態様によれば、本発明の剤の一回の経口摂取単位量を、アルコールの摂取前、摂取中または摂取後のいずれかにおいて少なくとも一回、対象に投与することが好ましい。
The administration schedule of the agent of the present invention can be appropriately set by those skilled in the art depending on the age, sex and symptoms of the subject as long as the effects of the present invention are not hindered. The agent of the present invention may be administered to a subject continuously or in a single dose. According to a preferred embodiment, it is preferable to administer a single oral intake unit amount of the agent of the present invention to the subject at least once before, during or after the intake of alcohol.
また、本発明の別の態様によれば、血中アセトアルデヒド濃度の上昇を抑制するための有効量の本発明の剤を、それを必要とする対象に摂取させることを含んでなる、悪酔いまたは二日酔いの防止方法が提供される。また、本発明の一つの態様によれば、悪酔いまたは二日酔いの防止方法は、ヒトに対する医療行為を除く。また、本発明の悪酔いまたは二日酔いの防止方法は、好ましくはアルコール代謝促進方法であり、より好ましくは、血中アセトアルデヒド濃度の上昇抑制方法である。ここで、「血中アセトアルデヒド濃度の上昇を抑制するための有効量」とは、上述の一回の経口摂取量単位の形態から構成することができる。また、「防止」には、確立された病態・症状を治療することだけでなく、将来確立される可能性のある病態・症状を予防することをも含む。
According to another aspect of the present invention, a sickness or hangover comprising ingesting an effective amount of the agent of the present invention for suppressing an increase in blood acetaldehyde concentration to a subject in need thereof. A prevention method is provided. Moreover, according to one aspect of the present invention, the method for preventing hangover or hangover excludes medical practice for humans. Moreover, the method for preventing hangover or hangover of the present invention is preferably a method for promoting alcohol metabolism, and more preferably a method for suppressing an increase in blood acetaldehyde concentration. Here, the “effective amount for suppressing an increase in the blood acetaldehyde concentration” can be composed of the above-mentioned single oral intake unit. In addition, “prevention” includes not only treating an established disease state / symptom, but also preventing a disease state / symptom that may be established in the future.
また、対象は哺乳動物、例えば、げっ歯類、イヌ、ネコ、ウシ、霊長類などであり、好ましくはヒトであり、より好ましくはアルコール摂取前、摂取中または摂取後のヒトである。また、対象は、健常人であっても病者であってもよいが、好ましくはアルコールの摂取前、摂取中または摂取後の健常人である。健常人としては、例えば、日本人間ドック学会の判定区分（２０１４年４月１日改訂）に基づき、血液検査の肝機能項目の結果が「Ａ」または「Ｂ」（「異常なし」または「軽度異常」）に分類される者が挙げられる。日本人間ドック学会の上記判定区分によれば、かかる健常人の血中肝機能パラメーターは、ＡＳＴ（ＧＯＴ）値は３５Ｕ／Ｌ以下であり、ＡＬＴ（ＧＰＴ）は４０Ｕ／Ｌ以下であり、γ－ＧＴＰ値は８０Ｕ／Ｌ以下の範囲を満たす。
The subject is a mammal, for example, a rodent, a dog, a cat, a cow, a primate, and the like, preferably a human, more preferably a human before, during or after alcohol intake. The subject may be a healthy person or a sick person, but is preferably a healthy person before, during or after taking alcohol. As a healthy person, for example, the liver function item result of blood test is “A” or “B” (“no abnormality” or “mild abnormality” based on the Judgment Category (revised April 1, 2014) )). According to the above judgment category of the Japan Ningen Dock Society, the blood liver function parameters of such healthy persons have an AST (GOT) value of 35 U / L or less, an ALT (GPT) of 40 U / L or less, and γ-GTP. The value satisfies the range of 80 U / L or less.
以下、実施例により本発明をより具体的に説明するが、本発明の技術範囲はこれらの例示に限定されるものではない。なお、特に指摘されない限り、本発明で用いられる全てのパーセンテージおよび比率は質量による。また、特に指摘されない限り、本明細書に記載の単位および測定方法は日本工業規格（ＪＩＳ規格）による。
Hereinafter, the present invention will be described more specifically by way of examples. However, the technical scope of the present invention is not limited to these examples. Unless otherwise indicated, all percentages and ratios used in the present invention are by weight. Unless otherwise indicated, the units and measurement methods described in this specification are based on Japanese Industrial Standards (JIS standards).
実施例１：マルスダレガイ目二枚貝の抽出物の製造
マルスダレガイ目二枚貝の濃縮液(Ocean Clam Concentrate/Sea Watch International, Ltd.、マルスダレガイ目二枚貝の取得地；アメリカのマサチューセッツからバージニアの海岸沖3～200マイルの海域)２２００ｇに４倍量の精製水８８００ｇを加水して希釈溶液を得た。次に、マルスダレガイ目二枚貝の濃縮液の0.08％相当のプロテアーゼ（天野エンザイム社製プロテアーゼP「アマノ」3SD 1.76g）およびペプチダーゼ（天野エンザイム社製ペプチダーゼR 1.76g）を添加し、３５℃で５時間攪拌して酵素分解処理した。次に、得られた酵素処理溶液を７５℃で２時間加熱して酵素失活および殺菌処理を行い、放冷した。得られた溶液１０９２５ｇを遠心分離（４２００rpm／１０min；日立工機社製himacCR7）し、分離した上清１０５６６ｇをろ過（メルク社製POLYSEP II 10”、1.2μm）し、ろ液１０３４４ｇを得た。さらに、得られたろ液を限外ろ過処理（ザルトリウス・ステディム・ジャパン社製SARTOCON Slice Cassette Hydrosart 100K）し、１７９４ｇまで濃縮した。なお、濃縮工程では、脱塩および精製のため、ろ液に加水して濃縮する操作を２回繰り返した。濃縮液は、スプレードライヤ（大川原化工機社製Ｌ－８i型／アトマイザ２５０００rpm １７０℃－８５℃）を用いて噴霧乾燥し、マルスダレガイ目二枚貝の抽出物粉末１９３ｇを得た。マルスダレガイ目二枚貝の抽出物粉末の成分分析を行ったところ、以下の通りであった。 Example 1: Manufacture of Marsdalegai bivalve extract (Ocean Clam Concentrate / Sea Watch International, Ltd., source of Marsdalegai bivalve; 3 to 200 miles off the coast of Virginia from Massachusetts, USA Sea area) 8200 g of 4 times amount of purified water was added to 2200 g to obtain a diluted solution. Next, 0.08% of protease (Amanoenzyme Protease P “Amano” 3SD 1.76g) and peptidase (Amanoenzyme Peptidase R 1.76g) equivalent to the concentrate of the bivalve bivalve are added, and at 35 ° C. for 5 hours. The mixture was stirred and subjected to enzymatic decomposition. Next, the obtained enzyme treatment solution was heated at 75 ° C. for 2 hours for enzyme deactivation and sterilization treatment, and then allowed to cool. 10925 g of the resulting solution was centrifuged (4200 rpm / 10 min; HimacCR7 manufactured by Hitachi Koki Co., Ltd.), and 10666 g of the separated supernatant was filtered (POLYSEP II 10 ″, 1.2 μm manufactured by Merck) to obtain 10344 g of filtrate. Further, the obtained filtrate was subjected to an ultrafiltration treatment (SARTOCON Slice Cassette Hydrosart 100K, manufactured by Sartorius Stedim Japan) and concentrated to 1794 g, which was added to the filtrate for desalting and purification. The concentrated solution was spray-dried using a spray dryer (L-8i type / Atomizer 25000 rpm 170 ° C.-85 ° C., manufactured by Okawara Chemical Industries Co., Ltd.), and 193 g of extract powder of the bivalve bivalve shellfish. When the component analysis of the extract powder of the bivalve bivalve was carried out, it was as follows.
マルスダレガイ目二枚貝の濃縮液(Ocean Clam Concentrate/Sea Watch International, Ltd.、マルスダレガイ目二枚貝の取得地；アメリカのマサチューセッツからバージニアの海岸沖3～200マイルの海域)２２００ｇに４倍量の精製水８８００ｇを加水して希釈溶液を得た。次に、マルスダレガイ目二枚貝の濃縮液の0.08％相当のプロテアーゼ（天野エンザイム社製プロテアーゼP「アマノ」3SD 1.76g）およびペプチダーゼ（天野エンザイム社製ペプチダーゼR 1.76g）を添加し、３５℃で５時間攪拌して酵素分解処理した。次に、得られた酵素処理溶液を７５℃で２時間加熱して酵素失活および殺菌処理を行い、放冷した。得られた溶液１０９２５ｇを遠心分離（４２００rpm／１０min；日立工機社製himacCR7）し、分離した上清１０５６６ｇをろ過（メルク社製POLYSEP II 10”、1.2μm）し、ろ液１０３４４ｇを得た。さらに、得られたろ液を限外ろ過処理（ザルトリウス・ステディム・ジャパン社製SARTOCON Slice Cassette Hydrosart 100K）し、１７９４ｇまで濃縮した。なお、濃縮工程では、脱塩および精製のため、ろ液に加水して濃縮する操作を２回繰り返した。濃縮液は、スプレードライヤ（大川原化工機社製Ｌ－８i型／アトマイザ２５０００rpm １７０℃－８５℃）を用いて噴霧乾燥し、マルスダレガイ目二枚貝の抽出物粉末１９３ｇを得た。マルスダレガイ目二枚貝の抽出物粉末の成分分析を行ったところ、以下の通りであった。 Example 1: Manufacture of Marsdalegai bivalve extract (Ocean Clam Concentrate / Sea Watch International, Ltd., source of Marsdalegai bivalve; 3 to 200 miles off the coast of Virginia from Massachusetts, USA Sea area) 8200 g of 4 times amount of purified water was added to 2200 g to obtain a diluted solution. Next, 0.08% of protease (Amanoenzyme Protease P “Amano” 3SD 1.76g) and peptidase (Amanoenzyme Peptidase R 1.76g) equivalent to the concentrate of the bivalve bivalve are added, and at 35 ° C. for 5 hours. The mixture was stirred and subjected to enzymatic decomposition. Next, the obtained enzyme treatment solution was heated at 75 ° C. for 2 hours for enzyme deactivation and sterilization treatment, and then allowed to cool. 10925 g of the resulting solution was centrifuged (4200 rpm / 10 min; HimacCR7 manufactured by Hitachi Koki Co., Ltd.), and 10666 g of the separated supernatant was filtered (POLYSEP II 10 ″, 1.2 μm manufactured by Merck) to obtain 10344 g of filtrate. Further, the obtained filtrate was subjected to an ultrafiltration treatment (SARTOCON Slice Cassette Hydrosart 100K, manufactured by Sartorius Stedim Japan) and concentrated to 1794 g, which was added to the filtrate for desalting and purification. The concentrated solution was spray-dried using a spray dryer (L-8i type / Atomizer 25000 rpm 170 ° C.-85 ° C., manufactured by Okawara Chemical Industries Co., Ltd.), and 193 g of extract powder of the bivalve bivalve shellfish. When the component analysis of the extract powder of the bivalve bivalve was carried out, it was as follows.
成分分析
水分 ７．３ｇ／１００ｇ（１０５℃／３ｈｒ乾燥）
タンパク質 １．６ｇ／１００ｇ（ケルダール法）
脂質 ０．２ｇ／１００ｇ（ソックスレー抽出法）
灰分 ０．６ｇ／１００ｇ（直接灰化法）
炭水化物 ９３．３ｇ／１００ｇ（計算式：１００－（水分＋タンパク質＋脂質＋灰分）
ナトリウム １６３ｍｇ／１００ｇ（原子吸光光度法）
グリコーゲン ７９．６ｇ／１００ｇ (ソモギー変法)
グルコース ９０．１ｇ／１００ｇ（高速液体クロマトグラフ法）
ムコ多糖 ０．４ｇ／１００ｇ（カルバゾール硫酸法）
ＤＮＡ ０．１２ｇ／１００ｇ (高速液体クロマトグラフ法)
ＲＮＡ ０．０４ｇ／１００ｇ (高速液体クロマトグラフ法)
重金属 (Pbとして) 検出せず（硫化ナトリウム比色法／定量下限１ppm）
一般細菌数（生菌数） ５．４×１０３／ｇ（標準寒天平板培養法）
大腸菌群 陰性／２．２２ｇ（ＢＧＬＢ法） Component analysis moisture 7.3 g / 100 g (105 ° C./3 hr dry)
Protein 1.6g / 100g (Kjeldahl method)
Lipid 0.2g / 100g (Soxhlet extraction method)
Ash content 0.6g / 100g (direct ashing method)
Carbohydrate 93.3 g / 100 g (Calculation formula: 100- (water + protein + lipid + ash)
Sodium 163mg / 100g (atomic absorption photometry)
Glycogen 79.6g / 100g (Modified Somogy)
Glucose 90.1g / 100g (high performance liquid chromatography)
Mucopolysaccharide 0.4g / 100g (carbazole sulfate method)
DNA 0.12g / 100g (High performance liquid chromatographic method)
RNA 0.04g / 100g (High performance liquid chromatography)
Heavy metal (as Pb) not detected (sodium sulfide colorimetric method / lower limit ofquantification 1 ppm)
General bacterial count (viable count) 5.4 × 10 3 / g (standard agar plate culture method)
Coliform group negative / 2.22g (BGLB method)
水分 ７．３ｇ／１００ｇ（１０５℃／３ｈｒ乾燥）
タンパク質 １．６ｇ／１００ｇ（ケルダール法）
脂質 ０．２ｇ／１００ｇ（ソックスレー抽出法）
灰分 ０．６ｇ／１００ｇ（直接灰化法）
炭水化物 ９３．３ｇ／１００ｇ（計算式：１００－（水分＋タンパク質＋脂質＋灰分）
ナトリウム １６３ｍｇ／１００ｇ（原子吸光光度法）
グリコーゲン ７９．６ｇ／１００ｇ (ソモギー変法)
グルコース ９０．１ｇ／１００ｇ（高速液体クロマトグラフ法）
ムコ多糖 ０．４ｇ／１００ｇ（カルバゾール硫酸法）
ＤＮＡ ０．１２ｇ／１００ｇ (高速液体クロマトグラフ法)
ＲＮＡ ０．０４ｇ／１００ｇ (高速液体クロマトグラフ法)
重金属 (Pbとして) 検出せず（硫化ナトリウム比色法／定量下限１ppm）
一般細菌数（生菌数） ５．４×１０３／ｇ（標準寒天平板培養法）
大腸菌群 陰性／２．２２ｇ（ＢＧＬＢ法） Component analysis moisture 7.3 g / 100 g (105 ° C./3 hr dry)
Protein 1.6g / 100g (Kjeldahl method)
Lipid 0.2g / 100g (Soxhlet extraction method)
Ash content 0.6g / 100g (direct ashing method)
Carbohydrate 93.3 g / 100 g (Calculation formula: 100- (water + protein + lipid + ash)
Sodium 163mg / 100g (atomic absorption photometry)
Glycogen 79.6g / 100g (Modified Somogy)
Glucose 90.1g / 100g (high performance liquid chromatography)
Mucopolysaccharide 0.4g / 100g (carbazole sulfate method)
DNA 0.12g / 100g (High performance liquid chromatographic method)
RNA 0.04g / 100g (High performance liquid chromatography)
Heavy metal (as Pb) not detected (sodium sulfide colorimetric method / lower limit of
General bacterial count (viable count) 5.4 × 10 3 / g (standard agar plate culture method)
Coliform group negative / 2.22g (BGLB method)
実施例２：マルスダレガイ目二枚貝の抽出物粉末の反復経口投与による血中アセトアルデヒド濃度上昇抑制作用の検討
ＳＤラット（７週齢、雄、日本チャールス・リバー株式会社製）を８日間の予備飼育した後、マルスダレガイ目二枚貝の抽出物粉末投与群と対照群の２群（ｎ＝６）に分けて本飼育（７日間）を実施した。抽出物粉末投与群では、注射用水（扶桑薬品工業株式会社）中、上記抽出物粉末を５０ｍｇ／ｍＬの濃度で溶解させた溶液を、１０ｍＬ／ｋｇの量で１日１回経口投与した（投与量５００ｍｇ／ｋｇ）。対照群では、注射用水を１０ｍＬ／ｋｇの量で１日１回投与した。７日間の経口投与が終了した１時間後、エタノール投与量が１ｇ／ｋｇとなるように２５％エタノール／生理食塩溶液を尾静脈内に投与した。エタノール投与後、０．５、１．０、１．５、２．０、３．０時間に、予めヘパリンナトリウム（ノボ・ヘパリン注１００００単位、持田製薬株式会社）を入れたディスポーザブルシリンジおよび針を用いて、無麻酔下で頸静脈から各時点血液約０．５ｍＬを採取した。得られた血液を等量の氷冷１mol/L過塩素酸と混和し、４℃、１２，０００ｇ×３分間遠心して上清を採取した。得られた上清は、血中エタノール濃度測定用サンプルと、血中アセトアルデヒド濃度測定用サンプルに小分けして分注し、測定時まで－８０℃で保存した。血中エタノール濃度測定はＦキットエタノール（株式会社 Ｊ．Ｋインターナショナル）を用いて行い、血中アセトアルデヒド濃度測定はＦキットアセトアルデヒド（株式会社Ｊ．Ｋ．インターナショナル）を用いて行った。測定結果の統計検定は、各群の等分散性の検定をF検定により行い、等分散の場合の群間比較はStudent- t検定で行い、不等分散の場合の群間比較は、Aspin-Welchの近似検定で行った。 Example 2: Examination of blood acetaldehyde concentration increase inhibitory effect by repeated oral administration of extract powder of bivalve bivalve mollusc , after pre-bred SD rats (7 weeks old, male, manufactured by Charles River Japan, Ltd.) for 8 days This breeding (7 days) was carried out by dividing into two groups (n = 6) of the extract powder administration group of the bivalve bivalve and the control group. In the extract powder administration group, a solution prepared by dissolving the extract powder at a concentration of 50 mg / mL in water for injection (Fuso Pharmaceutical Co., Ltd.) was orally administered once a day in an amount of 10 mL / kg (administration). Amount 500 mg / kg). In the control group, water for injection was administered once a day in an amount of 10 mL / kg. One hour after the completion of oral administration for 7 days, a 25% ethanol / physiological saline solution was administered into the tail vein so that the ethanol dosage was 1 g / kg. At 0.5, 1.0, 1.5, 2.0, and 3.0 hours after ethanol administration, a disposable syringe and needle in which heparin sodium (Novo-Heparin injection 10,000 units, Mochida Pharmaceutical Co., Ltd.) was placed in advance Used, approximately 0.5 mL of blood at each time point was collected from the jugular vein without anesthesia. The obtained blood was mixed with an equal amount of ice-cold 1 mol / L perchloric acid, centrifuged at 4 ° C., 12,000 g × 3 minutes, and the supernatant was collected. The obtained supernatant was aliquoted into a blood ethanol concentration measurement sample and a blood acetaldehyde concentration measurement sample, and stored at −80 ° C. until measurement. Blood ethanol concentration was measured using F kit ethanol (JK International Co., Ltd.), and blood acetaldehyde concentration was measured using F kit acetaldehyde (JK International Co., Ltd.). The statistical test of the measurement results is performed by F test for equal variance of each group, comparison between groups in case of equal variance is performed by Student-t test, and comparison between groups in case of unequal variance is Aspin- Welch's approximate test was performed.
ＳＤラット（７週齢、雄、日本チャールス・リバー株式会社製）を８日間の予備飼育した後、マルスダレガイ目二枚貝の抽出物粉末投与群と対照群の２群（ｎ＝６）に分けて本飼育（７日間）を実施した。抽出物粉末投与群では、注射用水（扶桑薬品工業株式会社）中、上記抽出物粉末を５０ｍｇ／ｍＬの濃度で溶解させた溶液を、１０ｍＬ／ｋｇの量で１日１回経口投与した（投与量５００ｍｇ／ｋｇ）。対照群では、注射用水を１０ｍＬ／ｋｇの量で１日１回投与した。７日間の経口投与が終了した１時間後、エタノール投与量が１ｇ／ｋｇとなるように２５％エタノール／生理食塩溶液を尾静脈内に投与した。エタノール投与後、０．５、１．０、１．５、２．０、３．０時間に、予めヘパリンナトリウム（ノボ・ヘパリン注１００００単位、持田製薬株式会社）を入れたディスポーザブルシリンジおよび針を用いて、無麻酔下で頸静脈から各時点血液約０．５ｍＬを採取した。得られた血液を等量の氷冷１mol/L過塩素酸と混和し、４℃、１２，０００ｇ×３分間遠心して上清を採取した。得られた上清は、血中エタノール濃度測定用サンプルと、血中アセトアルデヒド濃度測定用サンプルに小分けして分注し、測定時まで－８０℃で保存した。血中エタノール濃度測定はＦキットエタノール（株式会社 Ｊ．Ｋインターナショナル）を用いて行い、血中アセトアルデヒド濃度測定はＦキットアセトアルデヒド（株式会社Ｊ．Ｋ．インターナショナル）を用いて行った。測定結果の統計検定は、各群の等分散性の検定をF検定により行い、等分散の場合の群間比較はStudent- t検定で行い、不等分散の場合の群間比較は、Aspin-Welchの近似検定で行った。 Example 2: Examination of blood acetaldehyde concentration increase inhibitory effect by repeated oral administration of extract powder of bivalve bivalve mollusc , after pre-bred SD rats (7 weeks old, male, manufactured by Charles River Japan, Ltd.) for 8 days This breeding (7 days) was carried out by dividing into two groups (n = 6) of the extract powder administration group of the bivalve bivalve and the control group. In the extract powder administration group, a solution prepared by dissolving the extract powder at a concentration of 50 mg / mL in water for injection (Fuso Pharmaceutical Co., Ltd.) was orally administered once a day in an amount of 10 mL / kg (administration). Amount 500 mg / kg). In the control group, water for injection was administered once a day in an amount of 10 mL / kg. One hour after the completion of oral administration for 7 days, a 25% ethanol / physiological saline solution was administered into the tail vein so that the ethanol dosage was 1 g / kg. At 0.5, 1.0, 1.5, 2.0, and 3.0 hours after ethanol administration, a disposable syringe and needle in which heparin sodium (Novo-Heparin injection 10,000 units, Mochida Pharmaceutical Co., Ltd.) was placed in advance Used, approximately 0.5 mL of blood at each time point was collected from the jugular vein without anesthesia. The obtained blood was mixed with an equal amount of ice-cold 1 mol / L perchloric acid, centrifuged at 4 ° C., 12,000 g × 3 minutes, and the supernatant was collected. The obtained supernatant was aliquoted into a blood ethanol concentration measurement sample and a blood acetaldehyde concentration measurement sample, and stored at −80 ° C. until measurement. Blood ethanol concentration was measured using F kit ethanol (JK International Co., Ltd.), and blood acetaldehyde concentration was measured using F kit acetaldehyde (JK International Co., Ltd.). The statistical test of the measurement results is performed by F test for equal variance of each group, comparison between groups in case of equal variance is performed by Student-t test, and comparison between groups in case of unequal variance is Aspin- Welch's approximate test was performed.
図１に示される通り、マルスダレガイ目二枚貝の抽出物粉末投与群では、血中アセトアルデヒド濃度（平均±標準誤差）の上昇は、対照群と比較して有意に抑制されていた（Student- t検定、*:p<0.05、**:p<0.01 vs 対照群）。
As shown in FIG. 1, the increase in blood acetaldehyde concentration (mean ± standard error) was significantly suppressed in the extract powder administration group of Marsdalena bivalve extract compared to the control group (Student- t test, *: p <0.05, **: p <0.01V vs. control group).
実施例３：マルスダレガイ目二枚貝の抽出物粉末の単回経口投与による血中アセトアルデヒド濃度上昇抑制作用の検討
ＳＤラット（７週齢、雄、日本チャールス・リバー株式会社）を８日間の予備飼育した後、マルスダレガイ目二枚貝の抽出物粉末投与群と対照群の２群（n=６）に分けて本飼育（１日間）を実施した。抽出物粉末投与群では、注射用水（扶桑薬品工業株式会社）中、上記抽出物粉末を５０ｍｇ／ｍＬの濃度で溶解させた溶液を、１０ｍL／ｋｇの量で１日１回経口投与した（投与量５００ｍｇ／ｋｇ）。対照群では、注射用水を１０ｍL／ｋｇの量で１日１回投与した。経口投与が終了した１時間後、エタノール投与量が１ｇ／ｋｇとなるように２５％エタノール／生理食塩溶液を尾静脈内に投与した。エタノール投与後、０．５、１．０、１．５、２．０、３．０時間に、予めヘパリンナトリウム（ノボ・ヘパリン注１００００単位、持田製薬株式会社）を入れたディスポーザブルシリンジおよび針を用いて、無麻酔下で頸静脈から各時点血液約０．５ｍＬを採取した。得られた血液を等量の氷冷１mol/L過塩素酸と混和し、４℃、１２，０００ｇ×３分間遠心して上清を採取した。得られた上清は、血中エタノール濃度測定用サンプルと、血中アセトアルデヒド濃度測定用サンプルに小分けして分注し、測定時まで－８０℃で保存した。血中エタノール濃度測定はＦキットエタノール（株式会社 Ｊ．Ｋインターナショナル）を用いて行い、血中アセトアルデヒド濃度測定はＦキットアセトアルデヒド（株式会社Ｊ．Ｋ．インターナショナル）を用いて行った。測定結果の統計検定は、各群の等分散性の検定をF検定により行い、等分散の場合の群間比較はStudent- t検定で行い、不等分散の場合の群間比較は、Aspin-Welchの近似検定で行った。 Example 3: Examination of inhibitory action on blood acetaldehyde concentration rise by single oral administration of extract powder of bivalve bivalve shellfish SD (7 weeks old, male, Japan Charles River Co., Ltd.) after preliminary breeding for 8 days This breeding (1 day) was carried out by dividing into two groups (n = 6) of the extract powder administration group of the bivalve bivalve and the control group. In the extract powder administration group, a solution prepared by dissolving the extract powder at a concentration of 50 mg / mL in water for injection (Fuso Pharmaceutical Co., Ltd.) was orally administered once a day in an amount of 10 mL / kg (administration). Amount 500 mg / kg). In the control group, water for injection was administered once a day in an amount of 10 mL / kg. One hour after the completion of oral administration, a 25% ethanol / physiological saline solution was administered into the tail vein so that the ethanol dosage was 1 g / kg. At 0.5, 1.0, 1.5, 2.0, and 3.0 hours after ethanol administration, a disposable syringe and needle in which heparin sodium (Novo-Heparin injection 10,000 units, Mochida Pharmaceutical Co., Ltd.) was placed in advance Used, approximately 0.5 mL of blood at each time point was collected from the jugular vein without anesthesia. The obtained blood was mixed with an equal amount of ice-cold 1 mol / L perchloric acid, centrifuged at 4 ° C., 12,000 g × 3 minutes, and the supernatant was collected. The obtained supernatant was aliquoted into a blood ethanol concentration measurement sample and a blood acetaldehyde concentration measurement sample, and stored at −80 ° C. until measurement. Blood ethanol concentration was measured using F kit ethanol (JK International Co., Ltd.), and blood acetaldehyde concentration was measured using F kit acetaldehyde (JK International Co., Ltd.). The statistical test of the measurement results is performed by F test for equal variance of each group, comparison between groups in case of equal variance is performed by Student-t test, and comparison between groups in case of unequal variance is Aspin- Welch's approximate test was performed.
ＳＤラット（７週齢、雄、日本チャールス・リバー株式会社）を８日間の予備飼育した後、マルスダレガイ目二枚貝の抽出物粉末投与群と対照群の２群（n=６）に分けて本飼育（１日間）を実施した。抽出物粉末投与群では、注射用水（扶桑薬品工業株式会社）中、上記抽出物粉末を５０ｍｇ／ｍＬの濃度で溶解させた溶液を、１０ｍL／ｋｇの量で１日１回経口投与した（投与量５００ｍｇ／ｋｇ）。対照群では、注射用水を１０ｍL／ｋｇの量で１日１回投与した。経口投与が終了した１時間後、エタノール投与量が１ｇ／ｋｇとなるように２５％エタノール／生理食塩溶液を尾静脈内に投与した。エタノール投与後、０．５、１．０、１．５、２．０、３．０時間に、予めヘパリンナトリウム（ノボ・ヘパリン注１００００単位、持田製薬株式会社）を入れたディスポーザブルシリンジおよび針を用いて、無麻酔下で頸静脈から各時点血液約０．５ｍＬを採取した。得られた血液を等量の氷冷１mol/L過塩素酸と混和し、４℃、１２，０００ｇ×３分間遠心して上清を採取した。得られた上清は、血中エタノール濃度測定用サンプルと、血中アセトアルデヒド濃度測定用サンプルに小分けして分注し、測定時まで－８０℃で保存した。血中エタノール濃度測定はＦキットエタノール（株式会社 Ｊ．Ｋインターナショナル）を用いて行い、血中アセトアルデヒド濃度測定はＦキットアセトアルデヒド（株式会社Ｊ．Ｋ．インターナショナル）を用いて行った。測定結果の統計検定は、各群の等分散性の検定をF検定により行い、等分散の場合の群間比較はStudent- t検定で行い、不等分散の場合の群間比較は、Aspin-Welchの近似検定で行った。 Example 3: Examination of inhibitory action on blood acetaldehyde concentration rise by single oral administration of extract powder of bivalve bivalve shellfish SD (7 weeks old, male, Japan Charles River Co., Ltd.) after preliminary breeding for 8 days This breeding (1 day) was carried out by dividing into two groups (n = 6) of the extract powder administration group of the bivalve bivalve and the control group. In the extract powder administration group, a solution prepared by dissolving the extract powder at a concentration of 50 mg / mL in water for injection (Fuso Pharmaceutical Co., Ltd.) was orally administered once a day in an amount of 10 mL / kg (administration). Amount 500 mg / kg). In the control group, water for injection was administered once a day in an amount of 10 mL / kg. One hour after the completion of oral administration, a 25% ethanol / physiological saline solution was administered into the tail vein so that the ethanol dosage was 1 g / kg. At 0.5, 1.0, 1.5, 2.0, and 3.0 hours after ethanol administration, a disposable syringe and needle in which heparin sodium (Novo-Heparin injection 10,000 units, Mochida Pharmaceutical Co., Ltd.) was placed in advance Used, approximately 0.5 mL of blood at each time point was collected from the jugular vein without anesthesia. The obtained blood was mixed with an equal amount of ice-cold 1 mol / L perchloric acid, centrifuged at 4 ° C., 12,000 g × 3 minutes, and the supernatant was collected. The obtained supernatant was aliquoted into a blood ethanol concentration measurement sample and a blood acetaldehyde concentration measurement sample, and stored at −80 ° C. until measurement. Blood ethanol concentration was measured using F kit ethanol (JK International Co., Ltd.), and blood acetaldehyde concentration was measured using F kit acetaldehyde (JK International Co., Ltd.). The statistical test of the measurement results is performed by F test for equal variance of each group, comparison between groups in case of equal variance is performed by Student-t test, and comparison between groups in case of unequal variance is Aspin- Welch's approximate test was performed.
図２に示される通り、マルスダレガイ目二枚貝の抽出物粉末投与群では、血中アセトアルデヒド濃度（平均±標準誤差）の上昇は、対照群と比較して有意に抑制されていた（Student- t検定、*:p<0.05、**:p<0.01 vs 対照群）。
As shown in FIG. 2, the increase in blood acetaldehyde concentration (mean ± standard error) was significantly suppressed in the extract powder-administered bivalve bivalve extract powder compared to the control group (Student- t test, *: p <0.05, **: p <0.01V vs. control group).
実施例４：マルスダレガイ目二枚貝の抽出物粉末またはグルコースの反復経口投与による血漿中アセトアルデヒド濃度上昇抑制作用の検討
ＳＤラット（７週齢、雄、日本チャールス・リバー株式会社製）を８日間の予備飼育した後、マルスダレガイ目二枚貝の抽出物粉末投与群、グルコース投与群および対照群の３群（ｎ＝６）に分けて本飼育（７日間）を実施した。マルスダレガイ目二枚貝の抽出物粉末投与群では、注射用水（扶桑薬品工業株式会社）中、上記抽出物粉末を５０ｍｇ／ｍＬの濃度で溶解させた溶液を、１０ｍＬ／ｋｇの量で１日１回経口投与した（投与量５００ｍｇ／ｋｇ）。グルコース投与群では、グルコース水溶液（日本薬局方ぶどう糖注射液、グルコース濃度５％、大塚製薬製）を１日１回経口投与した（投与量５００ｍｇ／ｋｇ）。対照群では、注射用水を１０ｍＬ／ｋｇの量で１日１回投与した。７日間の経口投与が終了した１時間後、エタノール投与量が１ｇ／ｋｇとなるように２５％エタノール／生理食塩溶液を尾静脈内に投与した。エタノール投与後、０．５、２．０、４．０時間に、予めヘパリンナトリウム（ノボ・ヘパリン注１００００単位、持田製薬株式会社）を入れたディスポーザブルシリンジおよび針を用いて、無麻酔下で頸静脈から各時点血液約１．０ｍＬを採取した。得られた血液を遠心分離（１８００ｇ，４℃，１５分）し，血漿を分離し－８０℃で冷凍保管した。凍結融解させた血漿に等量の１ ｍｏｌ／Ｌ過塩素酸を添加・混和してさらに遠心分離し、上清を採取して半量の０．７ ｍｏｌ／Ｌりん酸三ナトリウムで中和処理したものを血漿中アセトアルデヒド濃度測定用サンプルとして用いた。血漿中アセトアルデヒド濃度測定はＦキットアセトアルデヒド（株式会社Ｊ．Ｋ．インターナショナル）を用いて行った。測定結果の統計検定は、各群の等分散性の検定をＦ検定により行い、等分散の場合の群間比較はStudent- t検定で行い、不等分散の場合の群間比較は、Aspin-Welchの近似検定で行った。 Example 4: Examination of inhibitory action on plasma acetaldehyde concentration increase by repeated oral administration of extract powder or glucose of bivalve bivalve shellfish SD rats (7 weeks old, male, manufactured by Charles River Japan, Inc.) for 8 days After that, this breeding (7 days) was carried out by dividing into 3 groups (n = 6) of the extract powder administration group, the glucose administration group and the control group of the bivalve bivalve. In the extract powder administration group of Marsdalegae bivalve, a solution of the extract powder dissolved in water for injection (Fuso Pharmaceutical Co., Ltd.) at a concentration of 50 mg / mL is orally administered once a day in an amount of 10 mL / kg. Administration (dose 500 mg / kg). In the glucose administration group, an aqueous glucose solution (Japanese Pharmacopoeia glucose injection solution, glucose concentration 5%, manufactured by Otsuka Pharmaceutical Co., Ltd.) was orally administered once a day (dose 500 mg / kg). In the control group, water for injection was administered once a day in an amount of 10 mL / kg. One hour after the completion of oral administration for 7 days, a 25% ethanol / physiological saline solution was administered into the tail vein so that the ethanol dosage was 1 g / kg. At 0.5, 2.0, and 4.0 hours after ethanol administration, a disposable syringe and needle containing heparin sodium (Novo-Heparin injection 10,000 units, Mochida Pharmaceutical Co., Ltd.) and a needle were used under anesthesia without anesthesia. Approximately 1.0 mL of blood at each time point was collected from the vein. The obtained blood was centrifuged (1800 g, 4 ° C., 15 minutes), and plasma was separated and stored frozen at −80 ° C. An equal amount of 1 mol / L perchloric acid was added to and mixed with freeze-thawed plasma, centrifuged, and the supernatant was collected and neutralized with half of 0.7 mol / L trisodium phosphate. The sample was used as a sample for measuring plasma acetaldehyde concentration. The plasma acetaldehyde concentration was measured using F kit acetaldehyde (JK International Co., Ltd.). The statistical test of the measurement results is performed by F test for equal variance of each group, the comparison between groups in the case of equal variance is performed by Student-t test, and the comparison between groups in the case of unequal variance is Aspin- Welch's approximate test was performed.
ＳＤラット（７週齢、雄、日本チャールス・リバー株式会社製）を８日間の予備飼育した後、マルスダレガイ目二枚貝の抽出物粉末投与群、グルコース投与群および対照群の３群（ｎ＝６）に分けて本飼育（７日間）を実施した。マルスダレガイ目二枚貝の抽出物粉末投与群では、注射用水（扶桑薬品工業株式会社）中、上記抽出物粉末を５０ｍｇ／ｍＬの濃度で溶解させた溶液を、１０ｍＬ／ｋｇの量で１日１回経口投与した（投与量５００ｍｇ／ｋｇ）。グルコース投与群では、グルコース水溶液（日本薬局方ぶどう糖注射液、グルコース濃度５％、大塚製薬製）を１日１回経口投与した（投与量５００ｍｇ／ｋｇ）。対照群では、注射用水を１０ｍＬ／ｋｇの量で１日１回投与した。７日間の経口投与が終了した１時間後、エタノール投与量が１ｇ／ｋｇとなるように２５％エタノール／生理食塩溶液を尾静脈内に投与した。エタノール投与後、０．５、２．０、４．０時間に、予めヘパリンナトリウム（ノボ・ヘパリン注１００００単位、持田製薬株式会社）を入れたディスポーザブルシリンジおよび針を用いて、無麻酔下で頸静脈から各時点血液約１．０ｍＬを採取した。得られた血液を遠心分離（１８００ｇ，４℃，１５分）し，血漿を分離し－８０℃で冷凍保管した。凍結融解させた血漿に等量の１ ｍｏｌ／Ｌ過塩素酸を添加・混和してさらに遠心分離し、上清を採取して半量の０．７ ｍｏｌ／Ｌりん酸三ナトリウムで中和処理したものを血漿中アセトアルデヒド濃度測定用サンプルとして用いた。血漿中アセトアルデヒド濃度測定はＦキットアセトアルデヒド（株式会社Ｊ．Ｋ．インターナショナル）を用いて行った。測定結果の統計検定は、各群の等分散性の検定をＦ検定により行い、等分散の場合の群間比較はStudent- t検定で行い、不等分散の場合の群間比較は、Aspin-Welchの近似検定で行った。 Example 4: Examination of inhibitory action on plasma acetaldehyde concentration increase by repeated oral administration of extract powder or glucose of bivalve bivalve shellfish SD rats (7 weeks old, male, manufactured by Charles River Japan, Inc.) for 8 days After that, this breeding (7 days) was carried out by dividing into 3 groups (n = 6) of the extract powder administration group, the glucose administration group and the control group of the bivalve bivalve. In the extract powder administration group of Marsdalegae bivalve, a solution of the extract powder dissolved in water for injection (Fuso Pharmaceutical Co., Ltd.) at a concentration of 50 mg / mL is orally administered once a day in an amount of 10 mL / kg. Administration (dose 500 mg / kg). In the glucose administration group, an aqueous glucose solution (Japanese Pharmacopoeia glucose injection solution, glucose concentration 5%, manufactured by Otsuka Pharmaceutical Co., Ltd.) was orally administered once a day (dose 500 mg / kg). In the control group, water for injection was administered once a day in an amount of 10 mL / kg. One hour after the completion of oral administration for 7 days, a 25% ethanol / physiological saline solution was administered into the tail vein so that the ethanol dosage was 1 g / kg. At 0.5, 2.0, and 4.0 hours after ethanol administration, a disposable syringe and needle containing heparin sodium (Novo-Heparin injection 10,000 units, Mochida Pharmaceutical Co., Ltd.) and a needle were used under anesthesia without anesthesia. Approximately 1.0 mL of blood at each time point was collected from the vein. The obtained blood was centrifuged (1800 g, 4 ° C., 15 minutes), and plasma was separated and stored frozen at −80 ° C. An equal amount of 1 mol / L perchloric acid was added to and mixed with freeze-thawed plasma, centrifuged, and the supernatant was collected and neutralized with half of 0.7 mol / L trisodium phosphate. The sample was used as a sample for measuring plasma acetaldehyde concentration. The plasma acetaldehyde concentration was measured using F kit acetaldehyde (JK International Co., Ltd.). The statistical test of the measurement results is performed by F test for equal variance of each group, the comparison between groups in the case of equal variance is performed by Student-t test, and the comparison between groups in the case of unequal variance is Aspin- Welch's approximate test was performed.
血漿中アセトアルデヒド濃度測定の結果は図３に示される通りであった。
マルスダレガイ目二枚貝の抽出物粉末投与群では、血漿中アセトアルデヒド濃度（平均±標準誤差）の上昇は、対照群およびグルコース投与群と比較して有意に抑制されていた（Aspin-Welchの近似検定、*:p<0.05、**:p<0.01 vs 対照群）。
マルスダレガイ目二枚貝の抽出物粉末を酸加水分解した場合、実施例１では、その分解物の約９０％がグルコースに当たっていた。これはマルスダレガイ目二枚貝の抽出物粉末がグルコースの多量体であるグリコーゲンを主成分として含有するためである。本実施例４の結果から、マルスダレガイ目二枚貝の抽出物粉末の血漿中アセトアルデヒド濃度上昇抑制効果は、マルスダレガイ目二枚貝の抽出物粉末が分解されたグルコースによるものでないことが確認された。 The results of measuring the plasma acetaldehyde concentration were as shown in FIG.
The increase in plasma acetaldehyde concentration (mean ± standard error) was significantly suppressed in the extract powder administration group of bivalve bivalve (Aspin-Welch approximate test, * : p <0.05, **: p <0.01 vs control group).
When the extract powder of the bivalve bivalve was acid hydrolyzed, in Example 1, about 90% of the decomposed product hit glucose. This is because the extract powder of the bivalve bivalve contains glycogen, which is a multimer of glucose, as a main component. From the results of Example 4, it was confirmed that the effect of suppressing the increase in the plasma acetaldehyde concentration of the extract powder of the bivalve bivalve was not due to the decomposed glucose of the extract powder of the bivalve bivalve.
マルスダレガイ目二枚貝の抽出物粉末投与群では、血漿中アセトアルデヒド濃度（平均±標準誤差）の上昇は、対照群およびグルコース投与群と比較して有意に抑制されていた（Aspin-Welchの近似検定、*:p<0.05、**:p<0.01 vs 対照群）。
マルスダレガイ目二枚貝の抽出物粉末を酸加水分解した場合、実施例１では、その分解物の約９０％がグルコースに当たっていた。これはマルスダレガイ目二枚貝の抽出物粉末がグルコースの多量体であるグリコーゲンを主成分として含有するためである。本実施例４の結果から、マルスダレガイ目二枚貝の抽出物粉末の血漿中アセトアルデヒド濃度上昇抑制効果は、マルスダレガイ目二枚貝の抽出物粉末が分解されたグルコースによるものでないことが確認された。 The results of measuring the plasma acetaldehyde concentration were as shown in FIG.
The increase in plasma acetaldehyde concentration (mean ± standard error) was significantly suppressed in the extract powder administration group of bivalve bivalve (Aspin-Welch approximate test, * : p <0.05, **: p <0.01 vs control group).
When the extract powder of the bivalve bivalve was acid hydrolyzed, in Example 1, about 90% of the decomposed product hit glucose. This is because the extract powder of the bivalve bivalve contains glycogen, which is a multimer of glucose, as a main component. From the results of Example 4, it was confirmed that the effect of suppressing the increase in the plasma acetaldehyde concentration of the extract powder of the bivalve bivalve was not due to the decomposed glucose of the extract powder of the bivalve bivalve.
実施例５：マルスダレガイ目二枚貝の抽出物粉末による悪酔い・二日酔いの防止作用の検討
被験者として、健常者１１名（男性９名、女性２名、年齢２３歳～５５歳）を選択した。日本人間ドック学会の判定区分（２０１４年４月１日改訂）によれば、被験者はいずれも、血液検査の肝機能項目が「Ａ」または「Ｂ」に分類される者であった。 Example 5: Examination of the action to prevent hangover and hangover by using extract powder of Bivalvia bivalve 11 healthy subjects (9 men, 2 women, age 23-55) were selected. According to the Judgment Category (revised on April 1, 2014) of the Japan Ningen Dock Society, all subjects were those whose liver function items in blood tests were classified as “A” or “B”.
被験者として、健常者１１名（男性９名、女性２名、年齢２３歳～５５歳）を選択した。日本人間ドック学会の判定区分（２０１４年４月１日改訂）によれば、被験者はいずれも、血液検査の肝機能項目が「Ａ」または「Ｂ」に分類される者であった。 Example 5: Examination of the action to prevent hangover and hangover by using extract powder of Bivalvia bivalve 11 healthy subjects (9 men, 2 women, age 23-55) were selected. According to the Judgment Category (revised on April 1, 2014) of the Japan Ningen Dock Society, all subjects were those whose liver function items in blood tests were classified as “A” or “B”.
試験開始に当たり、試験サンプルとして、ゼラチン製カプセル３個に計１０００ｍｇになるようにマルスダレガイ目二枚貝の抽出物粉末を充填したものを用意し、そのカプセルを３個（１０００ｍｇ）ずつ、番号（乱数）と試験日を記載した小袋に入れた。
また、プラセボサンプルとして、ゼラチン製カプセル３個に計１０００ｍｇになるようにデキストリン（パインデックス＃２、タピオカ由来、松谷化学工業製）を充填したものを用意し、そのカプセルを３個（１０００ｍｇ）ずつ、番号（乱数）と試験日を記載した小袋に入れた。
次に、試験サンプル、プラセボサンプルの入った２つの小袋をそれぞれ、１つのアルミ袋に入れた。
なお、２期から構成されるダブルブラインド試験を実施するため、アルミ袋に入った小袋のうち一方には１期目の試験日を記載し、他方には２期目の試験日を記載しておいた。これは、被験者が２期のうち一方で試験サンプルを摂取し他方でプラセボサンプルを摂取するように調整するためである。また、各期の各群の人数はそれぞれ５名又は６名になり、両期合計の各群の人数が同数になるように予め調整しておいた。 At the start of the test, prepare three gelatin capsules filled with extract powder of Marsdalena bivalve mollusk so that the total amount is 1000 mg. Each of these capsules (1000 mg), number (random number) and The test date was placed in a small bag.
As placebo samples, three gelatin capsules filled with dextrin (paindex # 2, derived from Tapioca, manufactured by Matsutani Chemical Industry Co., Ltd.) so that the total amount is 1000 mg are prepared, and three capsules (1000 mg) each. , Put in a pouch with number (random number) and test date.
Next, two sachets containing the test sample and placebo sample were each placed in one aluminum bag.
In order to carry out the double blind test consisting of two periods, one of the sachets contained in the aluminum bag shall contain the test date of the first period and the other shall contain the test day of the second period. Oita. This is to adjust the subject to take the test sample on one of the two phases and the placebo sample on the other. In addition, the number of people in each group in each period was 5 or 6, respectively, and the number of people in each group in both periods was adjusted in advance to be the same number.
また、プラセボサンプルとして、ゼラチン製カプセル３個に計１０００ｍｇになるようにデキストリン（パインデックス＃２、タピオカ由来、松谷化学工業製）を充填したものを用意し、そのカプセルを３個（１０００ｍｇ）ずつ、番号（乱数）と試験日を記載した小袋に入れた。
次に、試験サンプル、プラセボサンプルの入った２つの小袋をそれぞれ、１つのアルミ袋に入れた。
なお、２期から構成されるダブルブラインド試験を実施するため、アルミ袋に入った小袋のうち一方には１期目の試験日を記載し、他方には２期目の試験日を記載しておいた。これは、被験者が２期のうち一方で試験サンプルを摂取し他方でプラセボサンプルを摂取するように調整するためである。また、各期の各群の人数はそれぞれ５名又は６名になり、両期合計の各群の人数が同数になるように予め調整しておいた。 At the start of the test, prepare three gelatin capsules filled with extract powder of Marsdalena bivalve mollusk so that the total amount is 1000 mg. Each of these capsules (1000 mg), number (random number) and The test date was placed in a small bag.
As placebo samples, three gelatin capsules filled with dextrin (
Next, two sachets containing the test sample and placebo sample were each placed in one aluminum bag.
In order to carry out the double blind test consisting of two periods, one of the sachets contained in the aluminum bag shall contain the test date of the first period and the other shall contain the test day of the second period. Oita. This is to adjust the subject to take the test sample on one of the two phases and the placebo sample on the other. In addition, the number of people in each group in each period was 5 or 6, respectively, and the number of people in each group in both periods was adjusted in advance to be the same number.
試験１期目では、被験者は、小袋に記載の試験日に従ってサンプルをアルミ袋から選択し、飲料水１００ｍＬと共にサンプルを摂取した。サンプル摂取直後、各被験者は、全員同じ食事をしながら、通常飲酒する量よりもやや多い量のアルコール（２８～１４３ｇ、平均９４ｇ）を２～３時間かけて摂取した。
In the first test period, the subject selected a sample from an aluminum bag according to the test date described in the sachet, and ingested the sample together with 100 mL of drinking water. Immediately after taking the sample, all subjects took the same meal and took a slightly higher amount of alcohol (28 to 143 g, average 94 g) over the course of 2 to 3 hours.
アルコール摂取終了から約１０時間後の翌朝、「胃のムカツキ」、「吐き気・嘔吐」、「頭痛・頭重感」、「体のだるさ」、「眠気」、「筋肉痛」、「腸（下痢）」、「めまい・体の動揺感」という自覚症状に関し、各被験者は以下のスコアに基づく４段階評価を行った。
４点：ひどく有る
３点：まあまあ有る
２点：ほとんど無い
１点：全く無い The next morning, about 10 hours after the end of alcohol consumption, “stomach irritation”, “nausea / vomiting”, “headache / headache”, “dullness”, “sleepiness”, “muscle pain”, “intestine (diarrhea) Each subject gave a four-level evaluation based on the following scores regarding the subjective symptom of “vertigo” and “vertigo”.
4 points: severely 3 points: moderately acceptable 2 points: almostnone 1 point: not at all
４点：ひどく有る
３点：まあまあ有る
２点：ほとんど無い
１点：全く無い The next morning, about 10 hours after the end of alcohol consumption, “stomach irritation”, “nausea / vomiting”, “headache / headache”, “dullness”, “sleepiness”, “muscle pain”, “intestine (diarrhea) Each subject gave a four-level evaluation based on the following scores regarding the subjective symptom of “vertigo” and “vertigo”.
4 points: severely 3 points: moderately acceptable 2 points: almost
また、１期目の試験日の１週間後（ウオッシュアウト後）、２期目の試験を実施した。具体的には、被験者は、１期目と同じアルミ袋に残ったもう一方の小袋中のサンプルを飲料水１００ｍＬで摂取した。ここで、被験者には、サンプル摂取直後に１期目と同内容・同量の食事およびアルコール摂取を行うように予め指導しておいた。
アルコール摂取終了から約１０時間後に、各被験者は１期目と同様に自覚症状を評価した。 In addition, one week after the first test day (after washout), the second test was conducted. Specifically, the subject ingested the sample in the other sachet remaining in the same aluminum bag as in the first period with 100 mL of drinking water. Here, the subject was instructed in advance to take the same content and amount of meal and alcohol as in the first period immediately after taking the sample.
About 10 hours after the end of alcohol consumption, each subject evaluated subjective symptoms as in the first period.
アルコール摂取終了から約１０時間後に、各被験者は１期目と同様に自覚症状を評価した。 In addition, one week after the first test day (after washout), the second test was conducted. Specifically, the subject ingested the sample in the other sachet remaining in the same aluminum bag as in the first period with 100 mL of drinking water. Here, the subject was instructed in advance to take the same content and amount of meal and alcohol as in the first period immediately after taking the sample.
About 10 hours after the end of alcohol consumption, each subject evaluated subjective symptoms as in the first period.
上記２期の試験結果から、悪酔い・二日酔いの防止作用について検証を行った。
検証は、１期目および２期目において同内容・同量のアルコールを摂取することを遵守した７名（男性６名、女性１名：アルコール摂取量４２～１４３ｇ、平均１００ｇ）を対象とした。そして、試験サンプルを摂取した場合とプラセボサンプルを摂取した場合とに分けて、各評価項目のスコア平均を算出した。
結果は表１に示される通りであった。 From the test results of the above two periods, the effect of preventing hangover and hangover was verified.
The verification was conducted on 7 subjects (6 men and 1 woman: alcohol intake 42 to 143 g, average 100 g) that complied with the same content and the same amount of alcohol in the first and second phases. . Then, the average score of each evaluation item was calculated separately when the test sample was ingested and when the placebo sample was ingested.
The results were as shown in Table 1.
検証は、１期目および２期目において同内容・同量のアルコールを摂取することを遵守した７名（男性６名、女性１名：アルコール摂取量４２～１４３ｇ、平均１００ｇ）を対象とした。そして、試験サンプルを摂取した場合とプラセボサンプルを摂取した場合とに分けて、各評価項目のスコア平均を算出した。
結果は表１に示される通りであった。 From the test results of the above two periods, the effect of preventing hangover and hangover was verified.
The verification was conducted on 7 subjects (6 men and 1 woman: alcohol intake 42 to 143 g, average 100 g) that complied with the same content and the same amount of alcohol in the first and second phases. . Then, the average score of each evaluation item was calculated separately when the test sample was ingested and when the placebo sample was ingested.
The results were as shown in Table 1.
すべての評価項目において、マルスダレガイ目二枚貝の抽出物投与群のスコア平均値はプラセボ投与群のそれと比較して低値を示し、特に「胃のムカツキ」、「体のだるさ」については有意な差 (Paired-t検定、p<0.05)があることが確認された。
また、被験者ごとに全評価項目の合計スコアを算出した場合、４名の被験者において、プラセボ摂取と比較して、マルスダレガイ目二枚貝の抽出物摂取の方が２点以上低値を示した。この結果からも、悪酔い・二日酔いの緩和に対するマルスダレガイ目二枚貝の抽出物摂取の有効性が示唆された。 In all endpoints, the average score of the Marsdalena bivalve extract administration group was lower than that of the placebo administration group, especially for `` gastric irritations '' and `` body dullness '' (significant differences ( Paired-t test, p <0.05) was confirmed.
In addition, when the total score of all evaluation items was calculated for each subject, in the four subjects, the extract intake of the bivalve bivalve showed a lower value by 2 points or more than the placebo intake. This result also suggested the effectiveness of ingestion of Marsdalegai bivalve extract for alleviating hangover and hangover.
また、被験者ごとに全評価項目の合計スコアを算出した場合、４名の被験者において、プラセボ摂取と比較して、マルスダレガイ目二枚貝の抽出物摂取の方が２点以上低値を示した。この結果からも、悪酔い・二日酔いの緩和に対するマルスダレガイ目二枚貝の抽出物摂取の有効性が示唆された。 In all endpoints, the average score of the Marsdalena bivalve extract administration group was lower than that of the placebo administration group, especially for `` gastric irritations '' and `` body dullness '' (significant differences ( Paired-t test, p <0.05) was confirmed.
In addition, when the total score of all evaluation items was calculated for each subject, in the four subjects, the extract intake of the bivalve bivalve showed a lower value by 2 points or more than the placebo intake. This result also suggested the effectiveness of ingestion of Marsdalegai bivalve extract for alleviating hangover and hangover.
なお、２期目では、１期目と同内容・同量のアルコールを摂取することができなかった被験者が４名生じた。この４名のうち３名は、２期目にプラセボを摂取した被験者であった。この被験者３名は、プラセボを摂取した２期目よりも、マルスダレガイ目二枚貝の抽出物を摂取した１期目の方がアルコールを容易に摂取していたといえる。この結果もまた、マルスダレガイ目二枚貝の抽出物の摂取がアルコール代謝促進に影響を与えていることを示唆していると考えられる。
In the second period, four subjects were able to consume the same content and amount of alcohol as in the first period. Of these four, three were subjects who took placebo in the second term. It can be said that the three test subjects were more easily ingesting alcohol in the first period ingesting the extract of the bivalve bivalve than in the second period in which the placebo was ingested. This result also seems to suggest that the intake of the extract of the bivalve bivalve has an effect on the promotion of alcohol metabolism.
Claims (15)
- グリコーゲンを含有する、アルコール代謝促進剤。 Alcohol metabolism promoter containing glycogen.
- 前記グリコーゲンがマルスダレガイ目二枚貝の抽出物に由来する、請求項１に記載のアルコール代謝促進剤。 The alcohol metabolism promoter according to claim 1, wherein the glycogen is derived from an extract of a bivalve bivalve.
- 前記二枚貝がアイスランドガイである、請求項1または２に記載のアルコール代謝促進剤。 The alcohol metabolism promoter according to claim 1 or 2, wherein the bivalve is an Icelandic guy.
- マルスダレガイ目二枚貝の抽出物を含有する、アルコール代謝促進剤。 ア ル コ ー ル Alcohol metabolism promoter containing an extract of the bivalve bivalve.
- 前記二枚貝がアイスランドガイである、請求項４に記載のアルコール代謝促進剤。 The alcohol metabolism promoter according to claim 4, wherein the bivalve is an Icelandic guy.
- 一回の経口摂取量単位の形態である、請求項1～５のいずれか一項に記載のアルコール代謝促進剤。 The alcohol metabolism promoter according to any one of claims 1 to 5, which is in the form of a single oral intake unit.
- 血中アセトアルデヒド濃度の上昇抑制剤である、請求項１～６のいずれか一項に記載のアルコール代謝促進剤。 The alcohol metabolism promoter according to any one of Claims 1 to 6, which is an inhibitor of an increase in blood acetaldehyde concentration.
- 悪酔いまたは二日酔いの防止剤である、請求項1～７のいずれか一項に記載のアルコール代謝促進剤。 The alcohol metabolism promoter according to any one of claims 1 to 7, which is an agent for preventing hangover or hangover.
- 血中アセトアルデヒド濃度の上昇抑制方法であって、それを必要とする対象にグリコーゲンまたはマルスダレガイ目二枚貝の抽出物の有効量を摂取させることを含んでなる、方法。 A method for suppressing an increase in blood acetaldehyde concentration, which comprises ingesting an effective amount of an extract of glycogen or a bivalve bivalve in a subject in need thereof.
- アルコール代謝促進方法である、請求項９に記載の方法 The method according to claim 9, which is a method for promoting alcohol metabolism.
- 悪酔いまたは二日酔いの防止方法である、請求項９または１０に記載の方法 The method according to claim 9 or 10, which is a method for preventing hangover or hangover.
- 血中アセトアルデヒド濃度の上昇抑制剤の製造における、グリコーゲンまたはマルスダレガイ目二枚貝の抽出物の使用。 Use of an extract of glycogen or a bivalve bivalve in the production of a blood acetaldehyde concentration inhibitor.
- 前記剤がアルコール代謝促進剤である、請求項１２に記載の使用。 The use according to claim 12, wherein the agent is an alcohol metabolism promoter.
- 前記剤が悪酔いまたは二日酔いの防止剤である、請求項１２または１３に記載の使用。 The use according to claim 12 or 13, wherein the agent is an agent for preventing hangover or hangover.
- 血中アセトアルデヒド濃度の上昇抑制剤としての、グリコーゲンまたはマルスダレガイ目二枚貝の抽出物の使用。
Use of an extract of glycogen or a bivalve bivalve as an inhibitor of blood acetaldehyde levels.
Priority Applications (5)
| Application Number | Priority Date | Filing Date | Title |
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| JP2016557824A JP6681338B2 (en) | 2014-11-07 | 2015-11-06 | Alcohol metabolism promoter |
| EP15857073.9A EP3216455A4 (en) | 2014-11-07 | 2015-11-06 | Alcohol metabolism promoter |
| US15/525,053 US10478462B2 (en) | 2014-11-07 | 2015-11-06 | Alcohol metabolism promoter |
| CN201580060165.0A CN107073033A (en) | 2014-11-07 | 2015-11-06 | Alcohol metabolism accelerator |
| KR1020177012258A KR20170082527A (en) | 2014-11-07 | 2015-11-06 | Alcohol metabolism promoter |
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| JP2014-227387 | 2014-11-07 |
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| US (1) | US10478462B2 (en) |
| EP (1) | EP3216455A4 (en) |
| JP (1) | JP6681338B2 (en) |
| KR (1) | KR20170082527A (en) |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| JP2005261408A (en) * | 2004-03-16 | 2005-09-29 | Sasaki Shokuhin Kogyo Kk | Food containing fresh-water clam extract and having hepatic function improving effect and method for producing the same |
| WO2005102321A1 (en) * | 2004-04-19 | 2005-11-03 | Kirin Beer Kabushiki Kaisha | Composition for acceleration of alcohol metabolism or recuperation from fatigue through gluconeogenesis |
| JP2007210989A (en) * | 2006-02-08 | 2007-08-23 | Sasaki Shokuhin Kogyo Kk | Alcohol metabolism promoter |
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| US3471300A (en) * | 1966-08-08 | 1969-10-07 | Hca Food Corp | Process for treating clams |
| JP3793239B2 (en) | 1992-07-28 | 2006-07-05 | サントリー株式会社 | Inhibitor of acetaldehyde toxicity |
| NZ328489A (en) * | 1994-07-22 | 1999-06-29 | Mcfarlane Lab New Zealand Ltd | Extraction of glycogen from green lipped mussels and use as an anti-inflammatory agent |
| CN101232822B (en) | 2005-07-29 | 2012-11-14 | 蒂马基金会 | Composition for reducing the risc of ethanol metabolism and alcohol induced neuropathy |
| JP4974553B2 (en) | 2006-03-17 | 2012-07-11 | カゴメ株式会社 | Acetaldehyde metabolism promoter |
| US8889654B2 (en) * | 2009-08-03 | 2014-11-18 | Aziende Chimiche Riunite Angelini Francesco A.C.R.A.F. S.P.A. | Food formulation comprising glycogen |
| JP2011037790A (en) | 2009-08-13 | 2011-02-24 | Central Res Inst Of Electric Power Ind | Liver function-enhancing agent and functional food |
| KR101420795B1 (en) | 2012-12-07 | 2014-07-17 | 주식회사 비제이코리아 | Manufacturing method for baekhab soup |
| CN105491994A (en) * | 2013-04-26 | 2016-04-13 | 奇迹连结生物技术公司 | Monodisperse glycogen and phytoglycogen nanoparticles and use thereof as additives in cosmetics, pharmaceuticals, and food products |
-
2015
- 2015-11-06 EP EP15857073.9A patent/EP3216455A4/en not_active Withdrawn
- 2015-11-06 US US15/525,053 patent/US10478462B2/en active Active
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| Publication number | Priority date | Publication date | Assignee | Title |
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| JP2005261408A (en) * | 2004-03-16 | 2005-09-29 | Sasaki Shokuhin Kogyo Kk | Food containing fresh-water clam extract and having hepatic function improving effect and method for producing the same |
| WO2005102321A1 (en) * | 2004-04-19 | 2005-11-03 | Kirin Beer Kabushiki Kaisha | Composition for acceleration of alcohol metabolism or recuperation from fatigue through gluconeogenesis |
| JP2007210989A (en) * | 2006-02-08 | 2007-08-23 | Sasaki Shokuhin Kogyo Kk | Alcohol metabolism promoter |
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| See also references of EP3216455A4 * |
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| JP6681338B2 (en) | 2020-04-15 |
| CN107073033A (en) | 2017-08-18 |
| US10478462B2 (en) | 2019-11-19 |
| EP3216455A4 (en) | 2018-06-20 |
| US20170319630A1 (en) | 2017-11-09 |
| JPWO2016072496A1 (en) | 2017-08-31 |
| EP3216455A1 (en) | 2017-09-13 |
| KR20170082527A (en) | 2017-07-14 |
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